University of California, Davis CURRICULUM VITAE Name ... · 2010-pres Editor, Genetics in Medicine (Journal - Am College of Med Genetics and Genomics) Invited Presentations 1991

Rauen, K.A. 01-09-14

1

University of California, Davis CURRICULUM VITAE

Prepared: 01-09-14 Name: Katherine A. Rauen Position: Professor, Step 2

Department of Pediatrics, Division of Genomic Medicine

Address: UC Davis M.I.N.D. Institute Department of Pediatrics, Division of Genomic Medicine 2825 50th Street, Room 2248 Sacramento, CA, 95817 Voice: (916) 703-0382 Fax: (916) 703-0235 Email: [email protected]

EDUCATION

1977-1978 University of California, San Diego ---- ---- 1978-1981 California State University, Bakersfield B.S. m.c. laude Biology 1981-1985 University of California, Davis M.S. Physiology 1985-1992 University of California, Davis Ph.D. Genetics 1991-1995 University of California, Irvine M.D. Medicine 1995-1997 University of California, San Francisco Resident Pediatrics 1997-2000 University of California, San Francisco Fellow Medical Genetics CERTIFICATION and LICENSURE

Jun 1996 California Medical License A 60658 Oct 2000 American Board of Pediatrics Aug 2002 American Board of Medical Genetics Jan 2005 New York Medical License 234954-1 PRINCIPAL POSITIONS HELD

2000-2001 University of California, San Francisco Adjunct Instructor 2001-2007 University of California, San Francisco Assistant Adjunct Professor 2004- Stanford University, Palo Alto Adjunct Clinical Instructor 2007-2009 UCSF, Department of Pediatrics Associate Adjunct Professor 2007-2009 UCSF, Department of OB/Gyn and RS Associate Adjunct Professor 2007-2009 UCSF AFP Program Director 2007- UCSF NF/Ras Pathway Clinic Director 2008-2012 UCSF Medical Genetics Residency Associate Director 2009-2013 UCSF, Department of Pediatrics Associate Prof. In-Residence 2009- 2013 UCSF, Department of OB/Gyn and RS Associate Prof. In-Residence 2012-2013 UCSF Medical Genetics Residency Director 2013 UCSF Medical Genetics, Dept. Peds Interim Chief 2013 UCSF Medical Genetics, Dept. Peds Prof. In-Residence 2013 UCSF, Department of OB/Gyn and RS Prof. In-Residence 2013 UCSF AFP; CA Genetic Disease Branch Director 2014- UCSF, Department of Pediatrics Adjunct Professor 2014- UC Davis, Department of Pediatrics Professor 2014- UC Davis, Division of Genomic Medicine Chief

Rauen, K.A. 01-09-14

2

OTHER POSITIONS HELD CONCURRENTLY 1979-1981 California State University, Bakersfield Laboratory Assistant 1980 LAC/USC Medical Center, LA, CA Research Assistant 1982 SRI International, Menlo Park, CA Research Assistant 1982-1984 University of California, Davis Staff Research Associate I 1986-1989 University of California, Davis Staff Research Associate I 2001-2002 ONYX Pharmaceuticals, Richmond, CA Medical Research Consultant 2002-2013 UCSF Comprehensive Cancer Center Member 2003- Costello Syndrome Family Network Advisory Board 2004-2007 DNA Direct, San Francisco, CA Medical Director 2005-2013 UCSF Institute Human Genetics Member 2005- DECIPHER- Sanger Institute, UK Member 2005- CFC International Medical Advisor 2006- Costello Syndrome Family Network Co-Medical Director 2007-2009 UCSF AFP; CA Genetic Disease Branch Director 2007-2011 DNA Direct, San Francisco, CA Medical Advisor 2007- Pacific Reproductive Services Medical Consultant 2007-2013 UCSF Institute for Regeneration Medicine Member 2008- CTSA Child Health Oversight Committee Member 2008- NIH Rare Disease Workgroup Member 2009-2013 UCSF Scholarship Oversight Committee Member 2009- Assoc. Prof in Human and Med Genet Member 2009-2013 UCSF Molecular Genetics Path Fellowship Clinical Director 2010-2013 UCSF MFM/Genetics Fellowship Clinical Genetics Director 2010-2013 UCSF Medical Genet Curriculum Committee Member 2010- Genetic in Medicine (Journal of the ACMG) Editor 2011-2013 UCSF Peds Transition of Care Task Force Member 2011-2013 UCSF Mouse Path Core Oversight Committee Member 2012- March of Dimes- Scientific Review Member 2012- DOD NF Trials External Review Committee Member 2013 UCSF Genomic Medicine Governance Group Member 2013 UCSF Mission Bay Academic Bldg Committee Member 2013 UCSF T32 Genetics Training Program Director 2013 UCSF ABMG Laboratory Training Program Director HONORS AND AWARDS

1980 Bank of America Honorary Scholarship, California State University, Bakersfield 1981 Magna Cum Laude, California State University, Bakersfield 1983 Pacific Egg and Poultry Scholarship, UC Davis 1987 Pacific Egg and Poultry Scholarship, UC Davis 1989 Hubbard Farms Scholarship, UC Davis 1990 Jastro-Shields Graduate Research Scholarship, UC Davis 1991 Jastro-Shields Graduate Research Scholarship, UC Davis 1993 Medical Student American Cancer Society Research Grant, UC Irvine 1995 Gustave D. Suffin, M.D. Award, Outstanding Senior in Clinical Medicine, UC Irvine 2006 CFC International Achievement Award for Gene Discovery 2007 Costello Syndrome Family Network Award of Dedication 2007 CFC International Award of Service 2009 NF Inc Go the Extra Mile Award 2009 Award of Recognition-UCSF Department of OB/Gyn and Reproductive Sciences 2010 CFC International Award of Appreciation

Rauen, K.A. 01-09-14

3

2010 Award of Appreciation - Children’s Tumor Foundation 2011 Costello Syndrome Family Network Recognition of 10 Years of Service 2013 Presidential Early Career Awards for Scientists and Engineers KEYWORDS/AREAS OF INTEREST

Array CGH, cardio-facio-cutaneous syndrome, cancer genomics, cancer syndromes, clinical trials, Costello syndrome, constitutional chromosome aberrations, cytogenetics, congenital abnormalities, genetic medicine, medical education, mouse models, myogenesis, myopathy, neurofibromatosis 1, Noonan syndrome, prenatal genetics, RASopathy, Ras/MAPK pathway, small molecule inhibitors, signal transduction PROFESSIONAL ACTIVITIES Clinical 2000-2013 Attending Physician, UCSF Pediatrics in-patient and out-patient services 2007-2009 AFP Program Director, UCSF OB/Gyn and Reproductive Services 2007-pres Clinical Director, UCSF NF/Ras Pathway Clinic. 2013 AFP Program Director, UCSF OB/Gyn and Reproductive Services 2013 Interim Chief, Division of Medical Genetics, UCSF Dept. Pediatrics Summary of Clinical Service

Attending, Medical Genetics, UCSF: I attend for both the Biochemical Genetics and Dysmorphology services for a minimum of 2 months per year (25%+ time), supervising genetic resident/fellows, rotation pediatric residents and medical students. Although most of my out-patient service is in the NF/Ras Pathway Genetics Clinic, I still may also attend in General Genetics Clinic, Prenatal Genetics Clinic, Cancer Risk and Neurometabolic Clinic. Clinical Director, NF/Ras Pathway Clinic. In 2007, I created a new pathway-based clinic and novel clinical model which encompasses syndromes of the Ras/MAPK pathway, ‘RASopathies”. The mission of this clinic is to provide a multidisciplinary approach to the diagnosis and care of individuals with Neurofibromatosis types 1 and 2, Noonan/LEOPARD, CFC, Costello, Legius syndromes and others, or individuals with a phenotype which is suggestive of a diagnosis in this pathway. This clinic has become extremely successful. I created a UCSF Ras Pathway Provider Network and have over 60 UCSF physicians in both pediatric and adult medicine who are members of this provider network. This clinic has become so successful globally that several other medical centers have adopted my model for RASopathy patients. Professional Organizations

1989-1992 Sigma Xi 1991-pres American Medical Association 1995-2002 American Academy of Pediatrics 1996-pres American Society of Human Genetics 1998-2003 American Society of Gene Therapy 1998-pres American College of Medical Genetics 2000-pres Western Society for Pediatric Research 2009-pres Society for Pediatric Research 2009-pres Association of Professors in Human and Med Genetics Service to Professional Publications

Rauen, K.A. 01-09-14

4

1998-pres Ad hoc referee for American Journal of Medical Genetics, BioEssays, Cancer Research, Clinical Genetics, Journal of Clinical Oncology, Journal of Urology,

Prenatal Genetics, Expert Review of Molecular Diagnostics, BMC Medical Genetics, European Journal of Pediatrics, Oncogene, Nature Genetics, Human Molecular Genetics, Journal of Clinical Investigation, Genes Chromosome and Cancer, Genetics in Medicine, Nature Review Genetics

2003 Abstract Reviewer for American Society of Gene Therapy, annual meeting 2003 2009 Abstract Reviewer for American Society of Human Genetics, annual meeting 2009 2010-pres Editor, Genetics in Medicine (Journal - Am College of Med Genetics and Genomics) Invited Presentations

1991 Seminars in Animal Science, UC Davis 2001 The 2nd International Costello Syndrome Family Forum, Toronto, Canada 2002 Medical Genetics Seminar Series, Stanford Medical Center 2003 UCSF Pediatric Grand Rounds, UCSF Medical Center 2003 Department of Medical Genetics, Kaiser of Northern California at Oakland 2003 Pediatric Grand Rounds, Department of Pediatrics, Kaiser San Francisco 2003 Pediatric Grand Rounds, Children’s Hospital and Research Center, Oakland, CA 2004 FYI Seminar Series, Medical Genetics, Kaiser of No. California at Santa Teresa 2004 Pacific Southwestern Regional Genetics Seminar, Stanford Medical Center 2004 American Academy of Pediatrics, San Francisco, Moscone Center (Plenary) 2004 American Academy of Pediatrics, Selected Subject Session, SF, Moscone Center 2004 Synergy 2004, High Risk Obstetric and Neonatal Nursing Conference, UCSF,

Miyako Hotel San Francisco 2005 The 4th International Costello Syndrome Family Forum, St. Louis University 2005 Pediatric Grand Rounds, Department of Pediatrics, Sutter Hospital, Santa Rosa, CA 2005 Cell & Molecular Biology Colloquium, San Francisco State University, CA 2006 DECIPHER, Wellcome Trust Sanger Institute, Hinxton, England. 2006 CFC and Noonan Syndrome International Symposium, Potomac, MD 2007 Children’s Hospital of the Kings Daughter, Eastern VA Medical School 2007 American College of Medical Genetics National Meeting, Nashville, TN 2007 DECIPHER, Wellcome Trust Sanger Institute, Hinxton, England. 2007 Duke University School of Medicine, Durham NC 2007 CFC International Conference, Orlando, FL 2007 The 5th International Costello Syndrome Family Forum, Portland, OR 2007 Oregon Heath Sciences University, Department of Pediatrics, Portland OR 2007 1st International Costello Syndrome Research Symposium, Portland, OR 2007 57th Annual Meeting American Society of Human Genetics, San Diego, CA 2008 CTF Neurofibromatosis Symposium, Hyatt Hotel, Phoenix, AZ (Keynote) 2008 University of CA, San Francisco, Dept of Ob/Gyn and Reproductive Sciences 2008 University of CA, Davis Medical Center, Dept of Pediatrics, Sacramento, CA 2008 2008 CTF NF Conference, Bonita Springs, FL (Keynote) 2008 NF Inc Family Conference, University of California San Francisco, CA 2008 Children’s National Medical Center, Dept of Pediatrics, Washington DC 2009 University of CA, San Diego, Dept of Dermatology, La Jolla, CA 2009 University of CA, San Francisco, Dept of Pediatrics, San Francisco, CA 2009 MassGeneral/Harvard, Dept Pediatrics, Boston, MA 2009 2009 CTF NF Conference, Portland, OR (Speaker and Session Chair) 2009 The 6th International Costello Syndrome Family Forum, Berkeley, CA (Keynote) 2009 CFC International Conference, Berkeley, CA 2009 Genetic Syndromes of the Ras/MAPK Pathway, Berkeley, CA (Speaker and Chair) 2009 59th Annual Meeting ASHG, Honolulu, HA (invited session organizer and Speaker)

Rauen, K.A. 01-09-14

5

2010 Oxyopia Seminar, UC Berkeley School of Optometry, Berkeley, CA 2010 European Network on NS and Disorders. NSEuroNet Gothenburg, Sweden. 2010 Society of Pediatric Dermatology, Portland, OR 2010 American Academy of Pediatrics, San Francisco, CA 2010 Children’s Tumor Foundation, New Orleans, LA 2011 The 7th International Costello Syndrome Family Forum, Chicago, IL (Keynote) 2011 CFC International Conference, Chicago, IL 2011 Genetic Syndromes of the Ras/MAPK Pathway, Chicago, IL 2011 National Society of Genetic Counselors, San Diego, CA 2011 NF/Ras Clinic Open House and Mini-symposium, San Francisco, CA 2012 Rare Disease Day Research Symposium, Sanford Med Center, Sioux Falls, SD 2012 American College of Medical Genetics National Meeting, Charlotte, NC 2012 Workshop Birth Defects/Cancer:Intersect Genes/Prenatal Exposures, Atlanta, GA 2012 CFC International Consensus Meeting, South San Francisco, CA (Co-chair) 2013 UCSD Medical Center, Department of Medicine, La Jolla , CA 2013 The 8th International Costello Syndrome Family Forum, Orlando, FL 2013 CFC International Conference, Orlando, FL 2013 The 3rd International Genetic Syndromes of the Ras/MAPK Pathway, Orlando, FL 2013 International Meeting of Neurofibromatoses and RASopathies, Cardiff, UK Government and Other Professional Service

2005-pres CFC International Medical Board 2006-pres Costello Syndrome Family Network Co-Medical Director 2008-pres CTSA Pediatrics Oversight Committee Member 2008-pres NIH CC-CHOC Rare Disease Workgroup Member 2011 NIH StudySection R03,Brain Disorders and Clinical Neuroscience - Reviewer 2012-pres March of Dimes Scientific Reviewer 2012-pres DOD NF Trials External Review Committee Member UNIVERSITY SERVICE System-wide 1997-2002 Preceptor and Lecturer, Health and Medical Sciences 475, UC Berkeley 2000-2010 Lecturer, Medical Genetics, Children’s Hospital Oakland, Peds Resident Seminars 2001 Oral Examination Committee: Program in Genetic Counseling, UC Berkeley 2002 Preceptor, Independent Study: Program in Genetic Counseling, UC Berkeley 2009-pres Lecturer, Gene 274, Masters Program in Genetics Counseling, Stanford University 2009-pres Lecturer, Adv. Medical Genetics, Master in Genetics Counseling, CA State

Stanislaus 2011 Master’s Project Supervisor, Genetic Counseling Program, Stanford University UCSF Campus-wide 2009-2013 UCSF Molecular Genetics Pathology Fellowship, Clinical Director 2010-2013 UCSF Medical Genetics Curriculum Committee, Member 2011-2013 Mouse Pathology Core Oversight Committee, Member 2012 Institute Human Genetics-Genomic Initiative Task Force, Co-Chair 2013 UCSF Genomic Medicine Governance Group, Member School of Nursing 2003-2011 Lecturer, Medical Genetics for Nursing, Course N294B, UCSF Department of Pediatrics

Rauen, K.A. 01-09-14

6

2000-2013 Interviewer, Pediatric and Medical Genetics Residency Applicants, UCSF 2009-2013 Scholarship Oversight Committee, Dept of Pediatrics, UCSF 2011-2013 UCSF Pediatric Transition of Care Task Force PUBLIC SERVICE

2001-2008 Lecturer, Medical Genetics Lecture Series, Children’s Hospital and Research Center at Oakland, Pediatric Resident Seminars

2005-pres CFC International, Inc Medical Advisor 2006-pres Costello Syndrome Family Network Professional Advisory Board 2010-pres Genetic in Medicine (Journal of the ACMG) Editor 2012-pres March of Dimes- Scientific Committee Reviewer 2012 CFC Consensus Meeting Co-Chair TEACHING and MENTORING Effective teaching, education and mentoring are critical in an academic career. I have been continuously teaching since I was an undergraduate. Currently, I provide the didactic education for Medical Genetics to the pediatric residents at UCSF, Genetic Counseling masters students in the Stanford and CSU Stanislaus programs and lecture and lead small group discussion in Life Cycle for the 1st and 2nd year UCSF Medical Students. In the recent past, I did a 3-part lecture series on Medical Genetics for Pediatric Residents at Children’s Hospital Oakland and I give yearly lectures on Genetics and Gene Therapy in Course N294B--Medical Genetics for Nursing Students. I am invited to numerous formal lectures regionally, nationally and internationally each year. I mentor clinical fellows, pediatric residents, medical students and post-doctoral fellows in the clinical arena and the research arena, as well as have summer students and researchers join my lab. Please see Mentorship section. I am the Program Director for the UCSF Medical Genetics Residency, after serving 4 years as the programs Associate Director. In these roles, I maintain an educational environment conducive to educating the residents, oversee and ensure the quality of didactic and clinical education, and implemented policies and procedures consistent with the institutional and program requirements. In addition, I am the Clinical Director for the UCSF Molecular Genetics Pathology Fellowship and serve on the Medical Genetics Curriculum Committee for the School of Medicine. Formal Teaching/Lecturing Activities

1980-1981 Teaching Assistant, Human Physiology Laboratory, CSU Bakersfield 1983 Teaching Assistant, Systemic Animal Physiology Laboratory, UC Davis 1984 Teaching Assistant, Human Gross Anatomy Laboratory, UC Davis 1985 Teaching Associate, Developmental Genetics, UC Davis 1986 Teaching Associate, Systemic Animal Physiology Laboratory, UC Davis 1997-2002 Preceptor and Lecturer, Health and Medical Sciences 475, UC Berkeley 1998 Discussion Leader, Pediatrics 100 Medical Genetics, UC San Francisco 2000-2002 Lecturer, Introduction to Pediatrics, Calif. College of Podiatric Medicine 2000-2010 Lecturer, Medical Genetics, Children’s Hospital Oakland, Peds Resident Seminars 2000-pres Lecturer, Medical Genetics, UCSF Pediatric Resident Seminars 2003-2011 Lecturer, Medical Genetics for Nursing, Course N294B--UCSF 2007-2013 Discussion Leader, Life Cycle Course, 1st/2nd year medical students, UCSF 2009-2013 Lecturer, Life Cycle Course, 2nd year medical students, UC San Francisco 2009-pres Lecturer, Gene 274, Maters Program in Genetics Counseling, Stanford University 2009-pres Lecturer, Adv. Medical Genetics, Master in Genetics Counseling, CA State Stanislaus

Rauen, K.A. 01-09-14

7

Teaching Hours Teaching Type Last Year Current Year Anticipated Formal 40 hours/year 40 hours/year 40 hours/year Clinical 350 hours/year 350 hours/year 350 hours/year Laboratory 200 hours/year 200 hours/year 200 hours/year Clinical Teaching

1995-1997 pediatric rounds teaching medical students on peds rotation 1997-2002 UC Berkeley counseling students child development, teaching rounds 1997-2013 UCSF medical genetics rounds teaching med students/residents on rotation 1997-2013 UCSF med genet clinic conference presentation of current topics, patients 1999-2013 clinical genetics-didactic lectures Pediatric Residents UCSF and CHO Teaching Awards 1986 Nominated for “Best” Teaching Assistant, UC Davis Predoctoral Students Supervised or Mentored

1989-1991 Melinda Dayhuff (M.S., UC Davis) Trained and supervised 2003 Diana Grochova Graduate Student Supervised summer work 2009 Anna Martinez UCSF Medical Student PACCTR Fellow 2010-2013 Alice Goodwin, DDS Graduate Student Dept Orofacial Sciences Postdoctoral Fellows and Residents Directly Supervised or Mentored

2002-2004 Sebrina Cheng, MD Medical Genetics Resident Clinical/Research Supervision 2004-2007 Ophir Klein,MD,PhD Medical Genetics Fellow Clinical/Research Supervision 2004-2005 Petra Swidler, MD Medical Genetics Fellow Clinical Supervision 2004-2006 M. Martin, MD Medical Genetics Fellow Clinical/Research Supervision 2004-2006 Grace Yoon, MD Medical Genetics Fellow Clinical/Research Supervision 2004-2006 John Tsai, MD Medical Genetics Fellow Clinical Supervision 2005-2007 Jonathan Holt, OD Medical Genetics Fellow Clinical Supervision 2005-2009 Susan Tran, MD MFM Fellow Clinical/Research Supervision 2006-2008 K. Bianco, MD Medical Genetics Fellow Clinical/Research Supervision 2006-2008 Dawn Siegel, MD Ped Dermatology Fellow Research Supervision 2007-2009 Brian Schaffer, MD Medical Genetics Fellow Clinical Supervision 2007-2008 C. FitzGerald, MD Medical Genetic Fellow Clinical/Research Supervision 2007-2009 S. Shankar, MD,PhD Medical Genetics Fellow Clinical/Research Supervision 2008-pres Jacob Hogue, MD Medical Genetics Fellow Clinical Supervision 2008-pres Angie Child, MD MFM/Genetics Fellow Clinical/Research Supervision 2009-2011 Karla Wagner, MD Medical Genetics Resident Clinical/Research Supervision 2009-2011 Divya Vats, MD Medical Genetics Resident Clinical Supervision 2010-2011 Stephanie Sottile Stanford GC Grad student Research Supervision 2010 Rashmi Jain, MD Medical Genetics Resident Clinical Supervision 2011-pres Ben Li, MD Medical Genetics Resident Clinical Supervision 2011-pres Chung Lee, MD Medical Genetics Resident Clinical Supervision 2011-2013 S.Krishnamurthi,MD Medical Genetics Resident Clinical Supervision 2011-pres B.Thompson,PhD Post-doctoral Fellow Research Supervision 2011-pres Gemma Rooney,PhD Post-doctoral Fellow Research Supervision 2012-2013 B. Mendelsohn,MD Medical Genetics Resident Clinical Supervision 2013 Marwan Ali, MD Medical Genetics Resident Clinical Supervision

Rauen, K.A. 01-09-14

8

2013 Teresa Sparks, MD Medical Genetics Resident Clinical Supervision 2013 Ahmad Alhariri, MD Medical Genetics Resident Clinical Supervision Visiting Research Scientists Mentored 2005 Giannoulis Fakis, PhD Lecturer-Scientist, Democritus University of Thrace Volunteer Summer Students Mentored 2006 Alex Kasman University of Puget Sound, Tacoma, Washington 2010-2011 Divya Donthi University of CA, Santa Cruz Technician Training and Supervision

1987-1991 Naomi Guse, SRAI 1998-2000 Carol Tilden, SRAII 1999 Xiaoli Zhang, SRAII 1999-2001 Jesse Isaacs, SRAII 2000-2002 Jason Le, SRAII 2001-2003 Anja Huq, SRAII 2003-2011 Anne Estep, SRAII 2009-2010 Clarice Bunag, SRAI 2012-2013 Divya Donthi, Laboratory Assistant SCIENTIFIC and PROFESSIONAL MEETNGS & WORKSHOPS International p53 International Workshop, 2000 DW Smith Workshop 2001, 2005, 2006, 2007 CFC Syndrome International Family Conference, 2007, 2009, 2011 International Costello Syndrome Family Conference, 2001, 2005, 2007, 2009, 2011 Oncolytic Viruses as Cancer Therapeutics, 2003 DECIPHER, 2006, 2007 CFC/NS International Research Symposium 2006 Costello Syndrome International Research Symposium 2007 NF CTF Research Conference 2008, 2009, 2011, 2012, 2013 Genetic Syndromes of Ras/MAPK Pathway 2009, 2011, 2013 National Society for Developmental Biology, 1992 American College of Medical Genetics, 2003, 2005, 2006, 2007, 2008, 2010, 2011, 2012, 2013 American Society of Human Genetics, 1996-2005, 2007- 2012 American Society of Gene Therapy, 1998, 1999, 2003 NCI Prostate Cancer Inter-SPORE Workshop, 2000, 2002 NCI GU SPORE Bladder Cancer Intergroup Meeting, 2002 NCI SPORE Workshop, 2001, 2002 ASCO/AACR Clinical Cancer Research Workshop, 2003 Association of Professors in Human and Med Genetics, 2009-2012 Regional Northern California Genetics Exchange, 2000-2003, 2006-2013 UCSF Comprehensive Cancer Center Retreat, 2000, 2001, 2002, 2003 Western Society Pediatric Research, 2006- 2013 RESEARCH and CREATIVE ACTIVITIES

Rauen, K.A. 01-09-14

9

Ongoing Research Support 1) 1R01 AR062165-01A1 (PI) 08/01/12-07/31/17 NIH/NIAMS The Role of Germline Mutations in the Ras/MAPK Pathway on Skeletal Myogenesis This project explores the mechanisms of RASopathy muscle development and disease and may reveal new targets for therapeutic intervention. Role: PI 2) 1DP2OD007449 (Weiss) 09/30/10-08/31/15 Dissecting Epistasis and Pleiotropy in Autism towards Personalized Medicine This project explores how genetic variants mediate disease risk and improve diagnosis, prognosis, prevention and treatment options for autism. Role: Collaborating Investigator Completed Research Support 1)T32 GM007085-34 (PI) 07/01/09-06/30/14 NIH/NIGMS Postdoctoral Training in Medical Genetics Provides research training in medical genetics to future leaders in human and medical genetics. Does not support PI or lab. Role: PI 2) Auxiliary, UCSF/Mt Zion Fund (PI) 05/01/09-12/31/13 NF/Ras Pathway Clinic Role: PI 3) CTSI-Multi-Center Planning Grant (PI) 01/01/10-06/30/11 Costello and CFC: The use of small molecule inhibitors Role: PI 4) NOVO Nordisk Educational Grant (PI) 07/01/09-06/31/10 Syndromes of the Ras/MAPK Pathway Role: PI 5) K23 HD048502 (PI) 01/15/05-12/31/09 NIH/NICHD Molecular Analysis of Costello Syndrome The goal of this project was to identify the molecular cause of Costello syndrome and proposed dysregulation of the Ras pathway as its cause. Role: PI

6) R13 HD061140 (PI) 05/01/09-12/31/10 NIH/ NICHD/NCI/ORD Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back Role: PI

7) UC Opportunity Award (PI) 06/01/09- 12/31/09 Syndromes of the Ras/MAPK Pathway Role: PI

8) CTSI-Technology Mini-symposium Grant (PI) 06/01/09-09/30/09 Syndromes of the Ras/MAPK Pathway Role: PI

Rauen, K.A. 01-09-14

10

9) R13 HD055817 (PI) 05/01/07-12/31/07 NIH/ NICHD/NINDS/NCI/ORD 1st International Costello Syndrome Research Symposium Role: PI

10) Canary Fund (Co-PI) 08/01/06-10/31/07 Genetic Investigation of Ovarian Cancer Cell Lines Role: Co-PI 11) Clinical Investigators Research Program (PI) 05/01/04-07/31/06 Molecular Analysis of Familial Cancer Role: PI 12) P50-CA89520 (Co-PI) 09/01/00-08/31/03 NIH/NCI Viral Therapy for Prostate Cancer The goal of this project was to develop oncolytic gene therapy for prostate cancer. Role: Co-PI 13) UCSF Research Evaluation and Allocation Committee (PI) 11/01/03-10/31/04 The Evaluation of Chromosome Aberrations as a cause of Congenital Heart Disease Utilizing array CGH Role: PI Peer Reviewed Publications

1. Dvorak J, JL Halverson, P Gulick, KA Rauen, UK Abbott, BJ Kelly and FT Shultz. 1992. cDNA cloning of a Z-linked and W-linked gene in gallinaceous birds. Journal of Heredity 83: 22-25.

2. Chan TA, CA Chu, KA Rauen, M Kroiher, SM Tatarewicz and RE Steele. 1994. Identification of a gene encoding a novel protein-tyrosine kinase containing SH2 domains and ankyrin-like repeats. Oncogene 9(4): 1253-1259.

3. Rauen KA, CS LeCiel, UK Abbott and NJ Hutchison. 1994. Localization of chicken phosphoglycerate kinase to chromosome 4p by fluorescence in situ hybridization. Journal of Heredity 85: 147-151. 4. Rauen KA, P Cotter, S Bitts, V Cox and M Golabi. 2000. Cardio-facio-cutaneous syndrome phenotype in an individual with an interstitial deletion of chromosome 12q. American Journal of Medical Genetics 93: 219-222.

5. Rauen KA and P Cotter. 2001. Candidate region for cardio-facio-cutaneous syndrome. American Journal of Medical Genetics 101: 173.

6. Rauen KA, M Golabi, L Lei, S Bitts and P Cotter. 2001. Tandem duplication mosaicism: Characterization of a mosaic dup(5p) and review. Clinical Genetics 60: 367-371.

7. Rauen KA, DG Albertson, D Pinkel and PD Cotter. 2002. An additional patient with del(12)(q21.2q22): Further evidence for a candidate region for cardio-facio-cutaneous syndrome? American Journal of Medical Genetics 110:51-56. 8. Rauen KA, D Sudilovsky, J Le, K Chew, B Hann, V Weinberg, L Schmitt and F McCormick. 2002. Expression of the coxsackie-adenovirus receptor (CAR) in normal prostate and in primary and

Rauen, K.A. 01-09-14

11

metastatic prostate carcinoma: Potential relevance to gene therapy. Cancer Research 62:2812-3818.

9. Sachs MD, KA Rauen, M Ramamurthy, JL Dodson, AM De Marzo, MJ Putzi, MP Schoenberg and R Rodriguez. 2002. Integrin �v and coxsackie adenovirus receptor (CAR) expression in clinical bladder cancer. Urology 60(3): 531-536. 10. Rauen KA and P Cotter. 2003. Cardio-facio-cutaneous syndrome and Del(12q). American Journal of Medical Genetics 116A: 411-412. 11. Rauen KA, M Golabi and PD Cotter. 2003. Fertility in a female with mosaic trisomy 8: Report and review of the literature. Fertility and Sterility 79: 206-208. 12. Anders M, R Hansen, RX Ding, FM Waldman, KA Rauen, MJ Bissell and WM Korn. 2003. Disruption of three-dimensional tissue integrity facilitates adenovirus infection by deregulating the coxsackie- and adenovirus receptor. PNAS 100:1943-1948. 13. Sheen VL, JW Wheless, A Bodell, E Braverman, PD Cotter, KA Rauen, O Glenn, K Weisiger, S Packman, CA Walsh and EH Sherr. 2003. Periventricular heteropia associated with chromosome 5p anomalies. Neurology 60: 1033-1036.

14. Dietz LG, AA Wylie, KA Rauen, SK Murphy, RL Jirtle and PD Cotter. 2003. Exclusion of maternal uniparental disomy of chromosome 14 in patients referred for Prader-Willi syndrome using a rapid methylation PCR assay. Journal of Medical Genetics 40: e46. 15. Tartaglia M, PD Cotter, G Zampino, BD Gelb and KA Rauen. 2003. Exclusion of PTPN11 mutations in Costello syndrome: Further evidence for distinct genetic etiologies for Noonan, cardio-facio-cutaneous and Costello syndromes. Clinical Genetics 63: 423-426. 16. Ki A, KA Rauen, LD Black, DR Kostiner, PL Sandberg, D Pinkel, DG Albertson, ME Norton and PD Cotter. 2003. A ring 21 chromosome and a satellited 1p in the same patient: novel origin for an ectopic NOR. American Journal of Medical Genetics 120A: 365-369. 17. Klein OD, PD Cotter, DG Albertson, D Pinkel, WE Tidyman, MW Moore and KA Rauen. 2004. Prader-Willi syndrome resulting from an unbalanced translocation: Characterization by array comparative genomic hybridization. Clinical Genetics 65:477-428. 18. Cheng SF, KA Rauen, D Pinkel, DG Albertson, PD Cotter. 2005. Xq Chromosome Duplication in Males: Clinical, Cytogenetic and Array CGH Characterization of a New Case and Review. American Journal of Medical Genetics 135A:303-313. 19. Bao Y, W Peng, A Verbitsky, J Chen, L Wu, KA Rauen, JA Sawicki. 2005. Human coxsackie adenovirus receptor (CAR) expression in transgenic mouse prostate tumors enhances adenoviral delivery of genes. Prostate 64(4):401-407. 20. Matsumoto K, SF Shariat, GE Ayala, KA Rauen, SP Lerner. 2005. Loss of coxsackie and adenovirus receptor is associated with pathologic features of aggressive bladder cancer and decreased survival. Urology 66(2):441-6. 21. Klein, OD, PD Cotter, AM Schmidt, DP Bick, WE Tidyman, DG Albertson, D Pinkel, KA Rauen. 2005. Interstitial deletion of chromosome 12q: Genotype-phenotype correlation of two patients utilizing array comparative genomic hybridization. American Journal of Medical Genetics 138(4):349-354.

Rauen, K.A. 01-09-14

12

22. Marsee DK, DD Vadysirisack, CD Morrison, ML. Prasad, C Eng, Q Duh, KA Rauen, RT Kloos, SM Jhiang. 2005. Variable expression of coxsackie-adenovirus receptor in thyroid tumors: Implications for adenoviral gene therapy. Thyroid 15(9):977-987. 23. Cotter, PD, H Nguyen, G Tung and KA Rauen. 2005. Incidence of Microduplication 22q11.2 in Patients Referred for FISH Testing for Velo-Cardio Facial and DiGeorge Syndromes. European Journal of Medical Genetics 13(12):1245-1246. 24. Glass IA, KA Rauen, E Chen, J Parkes, DG Alberston, D Pinkel, and PD Cotter. 2006. Ring Chromosome 15: Characterization by Array CGH. Human Genetics Jan;118(5):611-7. 25. Iglesias A, KA Rauen, DG Albertson, D Pinkel, PD Cotter. 2006. Duplication of distal 20q: Clinical, cytogenetic and array CGH characterization of a new case. Clinical Dysmorphology 15: 19-23. 26. Estep AL, WE Tidyman, MA Teitell, PD Cotter, KA Rauen. 2006. HRAS Mutations in Costello Syndrome: Detection of Constitutional Activating Mutations in Codon 12 and 13 and Loss of Wild-type Allele in Malignancy. American Journal of Medical Genetics Jan 1;140(1):8-16. 27. Rodriguez-Viciana P, O Tetsu, AL Estep, WE Tidyman, BA Conger, M Santa Cruz, F McCormick, KA Rauen. 2006. Germline mutations in genes within the MAPK cascade cause cardio-facio-cutaneous syndrome. Science. 311(5765):1287-90. Epub 2006 Jan 26 28. Ayala G, T Satoh, R Li, M Shalev, Y Gdor, E Aguilar-Cordova, A Frolov, TM Wheeler, BJ Miles, K Rauen, BS Teh, EB Butler, TC Thompson, D Kadmon. 2006. Biological Response Determinants in HSV-tk + Ganciclovir Gene Therapy for Prostate Cancer. Molecular Therapy. Apr;13(4):716-28. 29. Takagishi J, KA Rauen, T Drumheller, B Kousseff , M Sutcliffe. 2006. Chromosome 3p25 Deletion in a Mother and Daughter with Minimal Phenotypic Effect. American Journal of Medical Genetics 140(14):1587-93. 30. Korn WM, M Moncada, C Christian, M Lacher, A McMillan, KA Rauen, RS Warren, L Ferrell. 2006. Expression of the Coxsackievirus- and Adenovirus Receptor in Gastrointestinal Cancer Correlates with Tumor Differentiation. 2006. Cancer Gene Therapy. 13(8):792-797. 31. Rauen KA. Distinguishing Costello vs Cardio-facio-cutaneous Syndrome: BRAF Mutations in Patients with a Costello Phenotype. 2006. American Journal of Medical Genetics. 140A:1681-1683. 32. Rodriguez-Viciana P, O Tetsu, K Oda, J Okada, K Rauen, F McCormick. 2006. Cancer targets in the Ras Pathway. Cold Spring Harbor Symposia on Quantitative Biology 70: 461-467. 33. Zampino G, F Pantaleoni, C Claudio, G Cobellis, I Vasta, EA Pogna, A Delogu, A Selicorni, KA Rauen, R Weksberg, A Ballabio, BD Gelb, G Neri, M Tartaglia. 2007. Diversity, parental germline origin and phenotypic spectrum of de novo HRAS missense change in Costello syndrome. Human Mutation. 28(3): 265-272. 34. Rauen KA. 2007. HRAS and the Costello Syndrome. Clinical Genetics. 71(2): 101-108. 35. Terry SF, PF Terry, KA Rauen, J Uitto, LB Bercovitch. 2007. A new model for the research enterprise: Advocacy organizations as research organizations. Nature Reviews Genetics. 8: 157-164.

Rauen, K.A. 01-09-14

13

36. Klein, OD, PD Cotter, MW Moore, A Zanko, M Gilats, CJ Epstein, F Conte, KA Rauen. 2007. Interstitial Deletions of Chromosome 6q: Genotype-Phenotype Correlation Utilizing Array CGH. Clinical Genetics. 71(3): 260-266. 37. Tokuyasu TA, PD Cotter, R Segraves, J Harris, ME Elder, M Gonzales, D Pinkel, DG Albertson, KA Rauen. 2007. Detection of Single Clone Deletions Using Array CGH: Identification of Submicroscopic Deletions in the 22q11 Deletion Syndrome as a Model System. American Journal of Medical Genetics. 143A: 925-932 38. Estep AL, C Palmer, F McCormick, KA Rauen. 2007. Mutation Analysis of BRAF, MEK1 and MEK2 in 15 Ovarian Cancer Cell Lines: Implications for Therapy. PLoS One 2(12):e1279. 39. Yoon G, J Rosenberg, S Blaser, KA Rauen. 2007. Neurological Complications of the Cardio-facio-cutaneous Syndrome (CFC). Developmental Medicine and Child Neurology 49: 894-899. 40. Senawong T, J Phuchareon, O Ohara, F McCormick, KA Rauen, O Tetsu. 2008. Germline mutations of MEK in cardio-facio-cutaneous (CFC) syndrome are sensitive to MEK and RAF inhibition: Implications for therapeutic options. Human Molecular Genetics. 17(3): 419–430. 41. Lin AE, KA Rauen, KL Gripp, JC Carey. 2008. Clarification of Previously Reported Costello Syndrome Patients. American Journal of Medical Genetics 146(7):940-3. 42. Rauen, KA, Y Aoki, KW Gripp, Y Matsubara, VK Proud, P Hammond, JE Allanson, MA Delrue, ME Axelrad, AE Lin, DA Doyle, B Kerr, JC Carey, F McCormick, JA Silva, MW Kieran, A Hinek, TT Nguyen, L Schoyer. 2008. Molecular Aspects, Clinical Aspects and Possible Treatment Modalities for Costello Syndrome: Proceedings from the 1st International Costello Syndrome Research Symposium 2007 American Journal of Medical Genetics 146A(9):1205-1217. 43. Kerr B, JE Allanson, MA Delrue, KW Gripp, D Lacombe, AE Lin, KA Rauen. 2008. Diagnosis of Costello Syndrome: Role of HRAS Mutation Analysis and Clarification of Nomenclature American Journal of Medical Genetics 146A(9):1218-1220. 44. Rodriguez-Viciana P and KA Rauen. 2008. Biochemical Characterization of Novel Germline BRAF and MEK Mutations in Cardio-facio-cutaneous Syndrome. Methods in Enzymology 438:277-89. 45. Chen E, E Obolensky, KA Rauen, LG Shaffer, X Li. 2008. Cytogenetic and Array CGH Characterization of De Novo 1p36 Duplications and Deletion in a Patient With Congenital Cataracts, Hearing Loss, Choanal Atresia, and Mental Retardation American Journal of Medical Genetics 146A(21):2785-90. 46. Tidyman WE and Rauen KA. 2008. Clinical and Molecular Overview of Noonan Syndrome, Costello Syndrome and Cardio-facio-cutaneous Syndrome: Dysregulation of the Ras/MAPK Pathway. Expert Review in Molecular Medicine. Dec 9;10:e37. 47. Anastasaki C, AL. Estep, R Marais, KA Rauen, EE Patton. 2009. Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development, and are sensitive to small molecule inhibitors. Human Molecular Genetics Jul 15;18(14):2543-54. 48. Tidyman WE and Rauen KA. 2009. The RASopathies: Developmental syndromes of Ras/MAPK pathway dysregulation. Current Opinion in Genetics and Development Jun;19(3):230-6.

Rauen, K.A. 01-09-14

14

49. Rauen KA et al. 2010. Proceedings from the 2009 Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back. American Journal of Medical Genetics. Jan;152A:4-24. 50. J. Kissil, J Blakeley, R Ferner, S Huson, M Kalamarides, V Mautner, F McCormick, H Morrison, R Packer, V Ramesh, N Ratner, KA Rauen, D Stevenson, K Hunter-Schaedle, K North. 2010. What’s New in Neurofibromatosis? Proceedings from The 2009 NF Conference: New Frontiers. American Journal of Medical Genetics. Feb;152A(2):269-83.. 51. Pierpont EI, ME Pierpont, NJ Mendelsohn, AE Roberts, E Tworog-Dube, KA Rauen, MS Seidenberg. 2010. Effects of Germline Mutations in the Ras/MAPK Signaling Pathway on Adaptive Behavior: Cardiofaciocutaneous Syndrome and Noonan Syndrome. American Journal of Medical Genetics. 152A(3):591-600. 52. Rauen KA, WE Tidyman, AL Estep, S Sampath, HM Peltier, SJ Bale, Y Lacassie. Molecular and functional analysis of a novel MEK2 mutation in cardio-facio-cutaneous syndrome: Transmission through four generations. 2010. Am Journal of Medical Genetics. 152A(4):807-14. 53. Champion KJ, C Bunag, AL Estep, JR. Jones, CH Bolt, RC Rogers, KA Rauen*, DB Everman*

(*co-senior authors). 2010. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. Clinical Genetics. 79(5):468-74. 54. Siegel DH, J McKenzie, I Freiden KA Rauen. 2011. Dysregulation of Ras/MAPK Signaling in Epidermal Development: Dermatologic Findings in 61 Mutation Positive Individuals with Cardio-facio-cutaneous Syndrome. 2010 British Journal of Dermatology.164(3):521-9. 55. Lin AE, ME. Alexander, SD Colan, B Kerr, KA Rauen, J Noonan, J Baffa, E Hopkins, K Sol-Church, G Limongelli, MC Digilio, B Marino, AM Innes, Y Aoki, M Silberbach, M Delrue, S White, RM Hamilton, W O’Connor, PD Grossfeld, L Smoot, RF Padera, KW Gripp. 2011 Clinical, Pathological and Molecular Analyses of Cardiovascular Abnormalities in Costello Syndrome: Comparison with Other Ras/MAPK Pathway Syndromes. American Journal of Medical Genetics. 155(3):486-507. 56. Wat MM. D Veenma, J Hogue, AM. Holder, Z Yu, J Wat, N Hanchard, O Shchelochkov, CJ Fernandes, A Johnson, KP Lally, A Slavotinek, O Danhaive, T Schaible, SW Cheung, KA Rauen, V Tonk, JW Belmont, D Tibboel, A de Klein, B Lee, DA Scott. 2011. Genomic Alterations that Contribute to the Development of Isolated and Non-Isolated Congenital Diaphragmatic Hernia. Journal of Medical Genetics 48(5):299-307. 57. Tidyman WE, HS Lee, KA Rauen. 2011. Skeletal muscle pathology in Costello and cardio-facio-cutaneous syndromes: Developmental consequences of germline Ras/MAPK activation on myogenesis. American Journal of Medical Genetics. 157(2):104-14. 58. Rauen KA, A Banerjee, WR Bishop, JO Lauchle, F McCormick, M McMahon, T Melese, PN Munster, S Nadaf, RJ Packer, J Sebolt-Leopold, DH Viskochil. 2011. Costello and cardio-facio-cutaneous syndromes: moving toward clinical trials in RASopathies. American Journal of Medical Genetics. 157(2):136-46. 59. Sanford EF, K Bermudez-Wagner, L Jeng, KA Rauen, AM Slavotinek. 2011. Congenital Diaphragmatic Hernia in Smith-Magenis Syndrome: A possible locus at 17p11.2. American Journal of Medical Genetics. 155A(11):2816-20.

Rauen, K.A. 01-09-14

15

60. Siegel DH, Mann JA, Krol AL, KA Rauen. 2012. Dermatologic Phenotype in Costello Syndrome: Consequences of Ras Dysregulation in Development. British Journal of Dermatology. Mar;166(3):601-7. 61. Anastasaki C, KA Rauen, and EE Patton. 2012. Continuous and sub-optimal MEK inhibitor treatment of BRAF CFC syndrome in zebrafish. Disease Models and Mechanisms. Jul;5(4):546-52. doi: 10.1242/dmm.008672. Epub 2012 Feb 2. 62. Huang B, P Pearle, KA Rauen, PD Cotter. 2012. Prenatal Diagnosis of Supernumerary Marker Chromosomes Derived From Chromosome 6: Cytogenetic, Molecular Cytogenetic and Array CGH Characterization. American Journal of Medical Genetics. Jul;158A(7):1568-73. 63. Ortiz MV, S Skoda-Smith, KA Rauen, RW Allan, WB Slayton. 2012. Constitutional Ras Pathway Dysregulation: Juvenile Myelomonocytic Leukemia in a 16 year old with Noonan syndrome. Journal Pediatric Hematology and Oncology. Oct;34(7):569-72. 64. Stevenson, DA, S Allen, WE Tidyman, JC Carey, DH Viskochil, A Stevens, H Hanson, X Sheng, BA Thompson, M Okumura, K Reinker, B Johnson, KA Rauen. 2012. Peripheral Muscle Weakness in RASopathies: Handgrip Strength in Costello, Cardio-facio-cutaneous, Noonan and Neurofibromatosis Type 1 Syndromes. Muscle and Nerve. Sep;46(3):394-9. 65. Glaser TS, KA Rauen, LJB Jeng, AG De Alba Campomanes. 2013. Finding of a lipodermoid in a patient with Emanuel Syndrome: a syndrome genetically distinct, but phenotypically similar to Oculo-Auriculo-Vertebral spectrum (Goldenhar Syndrome). JAAPOS. Apr;17(2):211-3. 66. Goodwin AF, S Oberoi, M Landan, C Charles, J Groth, A Martinez, C Fairley, LA Weiss, WE Tidyman, OD Klein, KA Rauen. 2013. Craniofacial and Dental Development in Cardio-facio-cutaneous Syndrome: The Importance of Ras Signaling Homeostasis. Clinical Genetics. Jun;83 (6):539-544. PMID: 22907230 67. Nowaczyk MJM, BA Thompson, S Zeesman, U Moog, PA Sanchez-Lara, PL Magoulas, RE Falk, J Hoover Fong, DAS Batista, SM Amudhavalli, SM White, GE Graham, KA Rauen. 2013. Deletion of MAP2K2/MEK2: A novel mechanism for a RASopathy? Clinical Genetics. 2013 Feb 4. doi: 10.1111/cge.12116. [Epub ahead of print]. 68. Jelin A, J Chang, V Feldstein, KA Rauen. 2013. Prenatal Ultrasound and Molecular Diagnosis Elucidate the Prognosis of Pfeiffer Syndrome. Case Reports in Perinatal Medicine. Mar 2(1-2):51-55. 69. KA Rauen. The RASopathies. Annual Review of Genomics and Human Genetics. 2013; 14:355-69. doi: 10.1146/annurev-genom-091212-153523. Epub 2013 Jul 15. PMID:23875798. 70. Goodwin AF, WE Tidyman, AH Jheon, A Sharir1, X Zheng, C Charles, JA Fagin, M McMahon, TGH Diekwisch, B Ganss, KA Rauen, OD Klein. Abnormal Ras Signaling Negatively Regulates Enamel Formation. Human Molecular Genetics. Hum Mol Genet. 2013 Oct 6. [Epub ahead of print] PMID:24057668. 71. Adviento B, IL Corbin, F Widjaja, G Desachy, N Enrique, T Rosser, S Risi, EJ Marco, RL Hendren, CE Bearden, KA Rauen, LA Weiss. Autism Traits in the RASopathies. Journal of Medical Genetics. 2013 Oct 7. doi: 10.1136/jmedgenet-2013-101951. [Epub ahead of print] PMID:24101678.

Rauen, K.A. 01-09-14

16

72. Goodwin AF, S Oberoi, M Landan, C Charles, JC Massie, C Fairley, KA Rauen*, OD Klein* (*co-senior authors). Craniofacial and Dental Development in Costello Syndrome (CS). American Journal of Medical Genetics. In Press. 73. Piotrowski A, J Xie, AB Poplawski, YF Liu, A Gomes, P Madanecki, C Fu, MR Crowley, D Crossman, L Armstrong, D Babovic-Vuksanovic, A Bergner, JO Blakeley, AL Bloomingthal, M Daniels, H Feit, K Gardner, S Hurst, C Kobelka, R Nagy, KA Rauen, J Slopis, P Suwannarat, J Westman, BR. Korf, LM Messiaen. Germline loss-of-function mutations in LZTR1 cause an inherited disorder of multiple schwannomas in SMARCB1-negative patients. Nature Genetics. In Press. 74. Terry J, KA Rauen, MJM Nowaczyk. Fetal autopsy findings of cardiofaciocutaneous syndrome with a unique BRAF mutation. Pediatric and Developmental Pathology. In Press. 75. Pierpont MEM, PL Magoulas, S Adi, MI Kavamura, G Neri, J Noonan, EI Pierpont, K Reinker, A Roberts, S Shankar, J Sullivan, M Wolford, B Conger, M Santa Cruz, KA Rauen. Journal of Pediatrics. In Review. Other Peer Reviewed Publications

1) Rauen KA: Cardiofaciocutaneous Syndrome (September 2012) in: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2010. Available at http://www.genetests.org. Book Chapters

1) Rauen KA. Ras/MAPK Pathway and the Cardio-Facio-Cutaneous Syndrome. Inborn Errors of Development. 2nd Edition. CJ Epstein, RP Erickson, A Wynshaw-Boris (eds.). Oxford University Press, New York. 2008. 2) Tidyman WE and Rauen KA. Molecular Causes of Cardio-facio-cutaneous Syndrome. In: Monographs in Human Genetics. Volume 17: Noonan Syndrome and Related Disorders. A matter of deregulated Ras signaling. Schmid M. ed. KARGER Publishers. Freiburg, Germany. 2009. 3) Tidyman WE and Rauen KA. Mutational and Functional Analysis in Human Ras/MAPK Genetic Syndromes. In: MAP Kinase Signaling Protocols. R Seger ed. Humana Press 2010. 4) Tidyman W.E. and Rauen K.A. Mutational and functional analysis in human Ras/MAP kinase genetic syndromes. Methods in Molecular Biology. 2010. 661:433-447. 5) Shaffer BL and Rauen KA. Reproductive Genetics. The University of California Obstetrics and Gynecology Women's Health Review. 2012. 1st Edition, Ed. L Giudice. 6) Tidyman WE and Rauen KA. The RASopathies: Syndromes of Ras/MAPK Pathway Dysregulation. In: Neurofibromatosis Type 1: Molecular and Cellular Biology. M. Upadhyaya, D. Cooper, Eds Springer. Heidelberg, Germany. 2013 7) Tidyman WE and Rauen KA. Treatment of Neurodevelopmental Disorders: Targeting Neurobiological Mechanisms”. B.Moghaddam, R.Hagerman, R.Hendren, Eds. Oxford Press. In Press 2013 Abstracts and Presentations

Rauen, K.A. 01-09-14

17

1. Halverson J and KA Rauen. 1988. The molecular approach to poultry breeding. Proceeding of the 37th Western Poultry and Disease Conference, Davis, CA.

2. Rauen KA, J Halverson, J Dvorak and UK Abbott. 1989. RFLP analysis in the turkey (Meleagris gallopavo). UC Davis Genetics Research Conference, Fallen Leaf Lake, CA.

3. Rauen KA, CS LeCeil, NL Hutchison and UK Abbott. 1992. The localization of phosphoglycerate kinase on chromosome 4p in the chicken using fluorescence in situ hybridization. Society for Developmental Biology 51st Annual Symposium. Univ. of Seattle, WA.

4. Cotter PD, KA Rauen, L Li, S Bitts, V Cox and M Golabi. 1998. Molecular and cytogenetic characterization of a mosaic tandem duplication of chromosome 5. American Society of Human Genetics 48th Annual Meeting. Denver, CO. Am J Hum Genet 63: A130, 1998.

5. Rauen KA, S Bitts, PD Cotter, V Cox and M Golabi. 1999. Cardio-facio-cutaneous syndrome phenotype in an individual with an interstitial deletion of chromosome 12q. American Society of Human Genetics 49th Annual Meeting. San Francisco, CA. Am J Hum Genet 65: A356

6. Rauen KA, S Bitts, PD Cotter, V Cox and M Golabi. 2000. Cardio-facio-cutaneous syndrome phenotype in an individual with an interstitial deletion of chromosome 12q. Northern California Genetics Exchange 1st Annual Meeting. Palo Alto, CA.

7. Rauen KA, D Albertson and PD Cotter. 2001. CFC and the WWW: Update on the candidate region for cardio-facio-cutaneous syndrome. Northern California Genetics Exchange 2nd Annual Meeting. Madera, CA. 8. Rauen KA, D Sudilovsky, J Le, K Chew and F McCormick. 2001. Expression of the primary human adenovirus receptor (CAR) in prostate cancer: Relevance to treatment with adenovirus. NCI 9th SPORE Investigators’ Workshop. Omni Shoreham Hotel, Washington DC. 9. Chiaverotti TA, KA Rauen, J Kivelstadt, B Huey, DG Albertson and A Balmain. 2001. Identification and mapping of prostate cancer genes important in tumor progression using the TRAMP mouse model. NCI 9th SPORE Investigators’ Workshop. Omni Shoreham Hotel, Washington DC.

10. Rauen KA, DG Albertson, D Pinkel and PD Cotter. 2001. The search for submicroscopic deletions in patients with Costello syndrome. 2nd International Costello Conference Toronto, Ontario, Canada. 11. Rauen KA, DG Albertson, D Pinkel and PD Cotter. 2001. The search for submicroscopic deletions in patients with cardio-facio-cutaneous syndrome using high resolution comparative genomic hybridization microarrays. XXII David W. Smith Workshop on Malformations and Morphogenesis. Lake Arrowhead, CA.

12. Chiaverotti TA, J Kivelstadt, KA Rauen, DG Albertson, D Pinkel and A Balmain. 2001. Characterization of strain differences that can be used to map genetic modifiers of progression in the TRAMP model and analysis of somatic genetic changes in tumors. Jackson Laboratory Workshop in Modeling Human Prostate Cancer in Mice.

13. Rauen KA, DG Albertson, D Pinkel and PD Cotter. 2001. An additional patient with del(12)(q21.2q22): Further evidence for a candidate region for cardio-facio-cutaneous syndrome? American Society of Human Genetics 51st Annual Meeting. San Diego, CA. Am J Hum Genet 69: A295, 2001 14. Rauen KA, D Sudilovsky, J Le, K Chew, B Hann, V Weinberg and F McCormick. 2001. Expression of the coxsackie-adenovirus receptor in normal prostate and in prostate carcinoma. UCSF Comprehensive Cancer Center Retreat. Granlibakken Conference Center, Lake Tahoe, CA. 15. Christian C, M Anders, KA Rauen, D Sudilovsky and M Korn. 2001. Expression patterns of the coxsackie and adenovirus receptor (CAR) in colorectal and liver cancer: correlation with histological grade. UCSF Comprehensive Cancer Center Retreat. Granlibakken Conference Center, Lake Tahoe, CA.

16. Sachs MD, KA Rauen, M Ramamurthy, JL Dodson, H van der Poel, AM deMarzo, MP Schoenberg and R Rodriguez. 2002. Susceptibility of clinical bladder cancer to adenoviral therapy. American Urological Association. Orlando, Fl.

17. Sachs MD, KA Rauen, M Ramamurthy, JL Dodson, H van der Poel, AM deMarzo, MP Schoenberg and R Rodriguez. 2002. Integrin αv and coxsackie adenovirus receptor (CAR) expression in clinical bladder cancer. American Association of Cancer Research 93rd Annual Meeting. San Francisco, CA. 18. Giedlin M, J Vargas, L Finucane, K Venstrum, K Rauen, M Korn, S Freeman, B Randlev. 2002. Immunohistochemical analysis of coxsackie adenovirus receptor (CAR) expression on SCCHN tumor confirms tumor type as target for adenoviral-based therapy. American Society of Clinical Oncology, Orlando FL.

Rauen, K.A. 01-09-14

18

19. Sherr EH, PD Cotter, KA Rauen, O Glenn, K Weisiger and S Packman. 2002. Trisomy of 5pter as a novel cause of bilateral periventricular nodular heteropia and epilepsy: implications for cortical development and clinical diagnostic evaluation. American Society of Child Neurology. Ann Neurol 52: S149, 2002. 20. Rauen KA, D Albertson and PD Cotter. 2002. Genome-wide screen for submicroscopic chromosome aberrations in patients with Costello syndrome using array CGH. Northern California Genetics Exchange 3rd Annual Meeting. Stanford University, Palo Alto, CA.

21. Sherr EH, PD Cotter, KA Rauen, O Glenn, K Weisiger and S Packman. 2002. Trisomy of 5pter as a novel cause of bilateral periventricular nodular heteropia and epilepsy: implications for cortical development and clinical diagnostic evaluation. Northern California Genetics Exchange 3rd Annual Meeting. Stanford University, Palo Alto, CA. (Presentation)

22. Rauen KA, R Rodriguez, A De Marzo, P Carroll, V Weinberg and F McCormick. 2002. The coxsackie-adenovirus receptor is highly expressed in metastatic prostate cancer: Potential impact for adenoviral gene therapy. American Society of Human Genetics 52nd Annual Meeting, Baltimore, MA. Am J Hum Genet 71: A583. 23. Tidyman WE, C Manuguid and KA Rauen. Measurement of the muscle stretch reflex latency period using the bsic BIOPAC Student Lab computer program in an undergraduate human physiology laboratory course. 42nd American Society for Cell Biology Meeting. 2002. Molecular Biology of the Cell. 13:412a. 24. Cotter PD, SM Bitts, LG Dietz, DG Albertson, VA Cox and KA Rauen. 2002. Prader-Willi syndrome resulting from an unbalanced translocation: characterization by array CGH. American Society of Human Genetics 52nd Annual Meeting, Baltimore, MA.. Am J Hum Genet 71: A291. 25. Dietz LG, AA Wylie, KA Rauen, SK Murphy, RL Jirtle and PD Cotter. 2002. Exclusion of maternal uniparental disomy of chromosome 14 in patients referred for Prader-Willi syndrome using a rapid methylation PCR assay. American Society of Human Genetics 52nd Annual Meeting, Baltimore, MA . Am J Hum Genet 71: A553. 26. Rauen KA, R Segraves, J Harris, ME Elder, M Gonzales, DG Albertson, D Pinkel, PD Cotter. Validation study of high resolution array CGH for the detection of submicroscopic deletions in DiGeorge and velo-cardio-facial syndromes. American College of Medical Genetics and March of Dimes Birth Defects Foundation Annual Clinical Genetics Meeting, San Diego, CA, March 13-16, 2003. Genet. Med. 5: A232, 2003. 27. Norton ME, KA Rauen, R Segraves, DG Albertson, D Pinkel, PD Cotter. Prenatal diagnosis by microarray CGH analysis of direct preparations. American College of Medical Genetics and March of Dimes Birth Defects Foundation Annual Clinical Genetics Meeting, San Diego, CA, March 13-16, 2003. Genet. Med. 5: A206, 2003. 28. Cotter PD, D Pinkel, DG Albertson, KA Rauen. Application of array comparative genomic hybridization to clinical cytogenetics. American College of Medical Genetics and March of Dimes Birth Defects Foundation Annual Clinical Genetics Meeting, San Diego, CA, March 13-16, 2003. Genet. Med. 5: A205, 2003. 29. Matsumoto K, GE. Ayala, S Shariat, KA Rauen, R Li, A Vazina, SP Lerner. Loss of coxsackie-adenovirus receptor expression is associated with bladder cancer grade, stage and survival. American Urological Association Meeting, Chicago, IL Apr 26-30, 2003. 30. Bao Y, W Peng, A Verbitsky, J Chen, L Wu, KA Rauen, J Sawicki. Prostate-specific expression of human coxsackie adenovirus receptor (hCAR) in transgenic mice. American Society of Gene Therapy. Washington, DC. 2003. 31. Rauen KA, J Simko, V Weinberg, A De Marzo, P Carroll, R Rodriguez, F McCormick. 2002. The coxsackie-adenovirus receptor is highly expressed in metastatic prostate cancer: Potential impact for adenoviral gene therapy. American Society of Gene Therapy. Washington, DC. 2003. 32. Simko J, V Weinberg, PR Carroll, F McCormick and KA Rauen. Survey of coxsackie-adenovirus receptor (CAR) expression in the non-neoplastic genito-urinary tract: Implications for gene therapy using adenoviral vectors. American Society of Gene Therapy. Washington, DC. 2003. 33. Rauen KA, ME Norton, R Segraves, TA Tokuyasu, D Pinkel, DG Albertson and PD Cotter. Array comparative genomic hybridization: Applications in genetic medicine. 53rd Annual Meeting of the American Society of Human Genetics, Los Angeles, CA, November 4-8, 2003. Am. J. Hum. Genet. 73, 2003.

34. Albertson DG, KA Rauen, PD Cotter, R Segraves, TA Tokuyasu, J Harris, ME Elder, M Gonzales, D Pinkel. High-resolution array CGH: a validation study for the detection of submicroscopic deletions in DiGeorge and velo-cardio-facial syndromes. 53rd Annual Meeting of the American Society of Human Genetics, Los Angeles, CA, November 4-8, 2003.Am. J. Hum. Genet. 73, 2003.

Rauen, K.A. 01-09-14

19

35. Cotter PD, A Iglesias, KA Rauen, DG Albertson, D Pinkel. Duplication 20q: clinical, cytogenetic and array comparative genomic hybridization characterization of a new case. 53rd Annual Meeting of the American Society of Human Genetics, Los Angeles, CA, November 4-8, 2003. Am. J. Hum. Genet. 73, 2003. 36. Simko J, V Weinberg, PR Carroll, F McCormick and KA Rauen. Coxsackie-adenovirus receptor (CAR) expression in the genito-urinary tract. 53rd Annual Meeting of the American Society of Human Genetics, Los Angeles, CA, November 4-8, 2003. Am. J. Hum. Genet. 73, 2003. 37. Glass IA, E Chen, KA Rauen, D Pinkel, DG Albertson, PD Cotter. Ring 15 syndrome: clinical, cytogenetic and comparative genomic hybridization array characterization of two discordant de novo cases. 53rd Annual Meeting of the American Society of Human Genetics, Los Angeles, CA, November 4-8, 2003. Am. J. Hum. Genet. 73, 2003. 38. Owen R, PA Swidler, AM Slavotinek, KA Rauen, PD Cotter, S Packman. A case report of duplication of X-chromosome material in a 3-year-old male with minor dysmorphic features and developmental delay. Western Society of Pediatric Research Annual Meeting, Carmel, California. January 28 -31, 2004, Carmel, CA. 39. Klein OD, PD Cotter, A Weiss, D Bick, DG Albertson, D Pinkel, KA Rauen. Interstitial deletion of chromosome 12q: Genotype-phenotype correlation of two patients utilizing array comparative genomic hybridization. American College of Medical Genetics, 10th Annual Clinical Genetics Meeting, Kissimmee, FL, March 4-7, 2004. 40. Cheng S, KA Rauen, DG Albertson, D Pinkel, PD Cotter. Partial duplication of the X chromosome in males: New case and review. American College of Medical Genetics, 10th Annual Clinical Genetics Meeting, Kissimmee, FL, March 4-7, 2004. 41. Klein OD, PD Cotter, A Zanko, M Gilats, CJ Epstein, F Conte, D Pinkel, DG Albertson and Rauen KA. Interstitial deletions of chromosome 6q: Genotype-phenotype correlation of three patients utilizing array comparative genomic hybridization. 54th Annual Meeting of the American Society of Human Genetics, Toronto, Ontario, Canada. October 26-31, 2004. 42. Clark RD, CJ Curry, TC Drumheller, PD Cotter and KA Rauen. Apparent triplication of distal 1q: Redefined by array CGH. Western Society of Pediatric Research Annual Meeting, Carmel, California. February 2-5, 2005. 43. Martin M and KA Rauen. Presentation of Coagulopathy in Urea Cycle Disorders: Recommendations for Aggressive Monitoring and Correction in the Neonate. Society for Inherited Metabolic Disorders Annual Meeting, Asilomar Conference Center, Pacific Grove, California, March 6-9, 2005. Molecular Genetics and Metabolism. 44. Tsa YJ, J Jeung, S Packman, M Martin, KA Rauen. Potential Bariatric Surgery Complications: Neonatal and Maternal Vitamin B12 Deficiency. Society for Inherited Metabolic Disorders Annual Meeting, Asilomar Conference Center, Pacific Grove, California, March 6-9, 2005. Molecular Genetics and Metabolism. 45. Zanko AM, PD Cotter, DG Albertson, D Pinkel and KA Rauen. Derivative 9 Chromosome: Elucidation of a Complex Inversion/Deletion by Array CGH. American College of Medical Genetics, 11th Annual Clinical Genetics Meeting, Gaylord Texan Resort and Convention Center Dallas, TX, March 17-20, 2005. Genetics in Medicine. 46. Rauen KA, TA Tokuyasu, Cotter DG, D Pinkel and DG Albertson. 2005. Large scale genomic variation: Dissecting the human genome by array CGH. 26th David W. Smith Workshop on Malformations and Morphogenesis. Iowa City, Iowa, August 2-6, 2005.

47. Chen E, E Obolensky, KA Rauen, X Li. Further delineation of the mechanisms and regions of dosage imbalance in rearrangements of 1p36: A patient with duplication 1p36 presenting with choanal atresia, congenital cataracts and severe developmental delay. 26th David W. Smith Workshop on Malformations and Morphogenesis. Iowa City, Iowa, August 2-6, 2005. 48. Rauen KA, RC Gallagher, PD Cotter, AL Estep, GM Enns, MF Marmor. Submicroscopic genomic aberrations: RPGR and OTC contiguous gene deletion revealed by array CGH. 55th Annual Meeting of the American Society of Human Genetics, Salt Lake City, UT. October 26-30, 2005. 49. Cotter PD, H Nguyen, G Tung, KA Rauen. Incidence of Microduplication 22q11.2 in Patients Referred for FISH Testing for Velo-Cardio-Facial and DiGeorge Syndromes. 55th Annual Meeting of the American Society of Human Genetics, Salt Lake City, UT. October 26-30, 2005. 50. Rauen KA, AL Estep, WE Tidyman, M Teitell, PD Cotter. Cancer Syndromes in the Ras Pathway: HRAS mutations in Costello syndrome. Western Society of Pediatric Research Annual Meeting, Carmel, California. February 1-4, 2006.

Rauen, K.A. 01-09-14

20

51. Klein OD, PD Cotter, MW Moore, KA Rauen. Paternal origin for interstitial deletions of 6q: molecular analysis of three families. American College of Medical Genetics Annual Meeting, San Diego, CA, March 23-26, 2006. 52. Rauen KA, AL Estep, WE Tidyman, M Teitell, Cotter PD. Cancer syndromes in the Ras pathway: HRAS mutations in Costello syndrome. American College of Medical Genetics Annual Meeting, San Diego, CA, March 23-26, 2006. 53. Rauen KA. The Road from Costello Syndrome to CFC: Phenotypic Breadcrumbs Lead the Way. 2006. Clinical Genetics Exchange 7th Annual Meeting. Stanford University. Palo Alto, CA. 54. Rauen KA, PD Cotter, TA Tokuyasu, A L Estep, RL Davis, D Pinkel, DG Albertson. Array CGH: Application to clinical genetics. 2nd International DECIPHER Symposium, The Wellcome Trust Conference Centre, Hinxton, Cambridge, UK, June 18th-20th, 2006. 55. McCormick F, KA Rauen, O Tetsu, P Rodriguez-Viciana, WE Tidyman, M Macrae, V Phan, V Ding. 2006. Novel Regulators and effectors of the Ras pathway. International Neurofibromatosis Consortium, Hotel Jerome, Aspen CO. 56. Lin AE, KW Gripp, KA Rauen, B Kerr, V Kimonis, RV Lacro, J Moeschler, S Weindling, R Hamilton.2006. The heart of Costello syndrome: Analysis of HRAS mutation positive patients. XXVII David W. Smith Workshop on Malformations and Morphogenesis. Lake Arrowhead, CA.

57. Tran SE, PD Cotter, TA Tokuyasu, DG Albertson, D Pinkel, ME Norton, KA Rauen. 2006. Array CGH for Prenatal Diagnosis: A Ready-for-Prime-Time Player? XXVII David W. Smith Workshop on Malformations and Morphogenesis. Lake Arrowhead, CA. 58. Holt J, A Davis, P Rosenthal, L Bull, S Packman, KA Rauen. 2006. Is there a BAAT in the brain? Marked white matter volume loss, hypomyelination and germinolytic cysts in an infant with hypercholanemia and recurrent hypoglycemia: XXVII David W. Smith Workshop on Malformations and Morphogenesis. Lake Arrowhead, CA.

59. Rauen KA, P Rodriguez-Viciana, O Tetsu, WE Tidyman, AL Estep, F McCormick, BA Conger, M Santa Cruz. 2006. The Ras/MAPK Pathway: Cutaneous Clues to the Molecular Lesion. XXVII David W. Smith Workshop on Malformations and Morphogenesis. Lake Arrowhead, CA. 60. Rauen KA, P Rodriguez-Viciana, AL Estep, WE Tidyman. MAPK Pathway Mutations in CFC Syndrome: Delineation of Molecular Heterogeneity and Genotype-phenotype Correlation. 56th Annual Meeting of the American Society of Human Genetics, New Orleans, LA. October 9-13, 2006. 61. Li X, E Chen, E Obolensky, B Blumberg, S Woo, KA Rauen. Genomic microarray analysis in patients with chromosome 8q24.1 deletions with and without Langer-Giedion syndrome. American College of Medical Genetics Annual Clinical Genetics Meeting, Nashville, TN, March 21-25, 2007. 62. Rauen KA. CFC Syndrome: Genotype-Phenoytpe Correlation. American College of Medical Genetics Annual Clinical Genetics Meeting, Nashville, TN, March 21-25, 2007. 63. Rauen KA, PD Cotter, TA Tokuyasu, DG Albertson, D Pinkel, ME Norton. Prenatal Diagnosis of Direct Amniocytes and Chorionic Villi by Array CGH Analysis. 3rd International DECIPHER Symposium, The Wellcome Trust Conference Centre, Hinxton, Cambridge, UK, May 16th-18th, 2007. 64. Estep AL, C Palmer, F McCormick, KA Rauen. 2007. BRAF and MEK Mutations in Ovarian Cancer: Implications for Therapy. 2nd Annual Canary Foundation Meeting. Stanford University, Palo Alto, CA, May 23, 2007. 65. Rauen KA. Germline Mutations within the MAPK Pathway: How do they compare to Cancer? Clinical Genetics Exchange 8th Annual Meeting. UCSF, San Francisco, CA 2007 66. Bianco K, A Estep, T Tokuyasu, W Tidyman, D Wieczorek, PD Cotter and KA Rauen. Submicroscopic Copy Number Variation in Costello Syndrome: Genome Scanning by array CGH. XXVIII David W. Smith Workshop on Malformations and Morphogenesis. Williamsburg VA. August 2007. 67. Rauen KA. Germline Mutations within the MAPK Pathway: How do they compare to Cancer? XXVIII David W. Smith Workshop on Malformations and Morphogenesis. Williamsburg VA. August 2007

68. Rauen KA. The dermatologic phenotypes of the RAS/MAPK pathway. 57th Annual Meeting of the American Society of Human Genetics, San Diego Convention Center, San Diego, CA. October 23-27, 2007.

Rauen, K.A. 01-09-14

21

69. Rauen, KA, AL Estep and O Tetsu . Functional in vitro characterization of MEK mutations in CFC: Implications for therapeutic options. Western Society of Pediatric Research Annual Meeting, Carmel, California. January 30-February 3, 2008. 70. Tetsu O, Senawong T, J Phuchareon, O Ohara, F McCormick, KA Rauen. Cardio-facio-cutaneous syndrome germline mutations of MEK are sensitive to MEK and RAF inhibition: Implications for therapeutic options. 2008 AACR Annual Meeting in San Diego, CA. 71. Estep AL and KA Rauen. Cardio-facio-cutaneous syndrome: Moving towards therapeutic options. American College of Medical Genetics Annual Clinical Genetics Meeting, Phoenix, AZ, March 12-16, 2008. 72. Shankar SP, Rauen KA. Ophthalmic manifestiations in cardio-facio-cutaneous syndrome of the Ras/MAPK pathway. Department of Pediatrics Research Day, UCSF, May 30, 2008. 73. KA Rauen. Medical Genetics Syndromes of the Ras/MAPK Pathway: An Overview. 2008 NF Conference. Bonita Springs Fl; June 5-10, 2008 74. Anastasaki C, J Richardson, R Marais, KA Rauen, EE Patton. The MAPK signaling pathway in development and disease. 8th International Meeting on Zebrafish Development and Genetics 2008, June 25-29, Madison WS. 75. Shankar S, E Burner, T Young, Rauen KA. Genotype/phenotype Correlation of Ocular Manifestations in Cardio-facio-cutaneous Syndrome. 58th Annual Meeting of the American Society of Human Genetics, Philadelphia Convention Center, Philadelphia, PA. November 11-15, 2008. 76. Rauen KA. AL Estep, SJ Bale, WE Tidyman, Y Lacassie. Molecular and functional analysis of a novel MEK2 mutation in cardio-facio-cutaneous syndrome: Transmission through four generations. 58th Annual Meeting of the American Society of Human Genetics, Philadelphia Convention Center, Philadelphia, PA. November 11-15, 2008. 77 Lacassie Y, S Sampath, HM Peltier, S Bale, KA Rauen. Cardio-facio-cutaneous syndrome (CFCS) due to a novel MEK2 mutation involving four generations: Clinical delineation and natural history. 58th Annual Meeting of the American Society of Human Genetics, Philadelphia Convention Center, Philadelphia, PA. November 11-15, 2008. 78. Shankar S, T Young, E Burner, Rauen KA. Visual and auditory features in children with cardio-facio-cutaneous syndrome. Western Society of Pediatric Research Annual Meeting, Carmel, California. January 28- 31, 2009. 79. Tran SH, KA Rauen. Prenatal phenotype and neonatal presentation of cardio-facio-cutaneous syndrome. Society for Maternal-Fetal Medicine Annual Meeting. Manchester Grand Hyatt San Diego, CA, January 26- 31, 2009 80. Tran SH, KA Rauen. Prenatal phenotype and neonatal presentation of cardio-facio-cutaneous syndrome. American Institute of Ultrasound in Medicine 2009 Annual Convention, Marriott Marquis Hotel, New York City, New York, April 2-5, 2009. 81. Strecker MN, JM Puck, KA Rauen. The UCSF NF/Ras pathway clinic: A model for comprehensive and transition of care for a group of rare cancer syndromes. 2009 Pediatric Academic Societies Annual Meeting, May 2-5 2009 Baltimore, MD. 82. Shankar SP, TL Young, KA Rauen. Ocular Manifestations of Ras/MAPK Dysregulation: A Comparison of CFC, Costello, Noonan Syndromes, and Neurofibromatosis 1. Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back. Doubletree Hotel&Executive Meeting Center, Berkeley, CA, August 1–2, 2009. 83. Siegel DH, J McKenzie, KA Rauen. Dermatologic Findings in 55 Mutation Positive Individuals With Cardio-Facio-Cutaneous Syndrome. Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back. Doubletree Hotel&Executive Meeting Center, Berkeley, CA, August 1–2, 2009. 84. Tran SH, KA Rauen. Prenatal Phenotype and Neonatal Presentation of Cardio-Facio-Cutaneous Syndrome Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back. Doubletree Hotel&Executive Meeting Center, Berkeley, CA, August 1–2, 2009. 85. Strecker MN, KA Rauen. An Innovative Approach to Specialty Genetics: The UCSF NF/Ras Pathway Genetics Clinic. Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back. Doubletree Hotel&Executive Meeting Center, Berkeley, CA, August 1–2, 2009. 86. Jelin AC, C Herrick, J Chang, V Feldstein, M Strecker, KA Rauen. Fetal US and prenatal molecular diagnosis elucidate the prognosis for Pfeiffer syndrome. Western Society of Pediatric Research Annual Meeting, Carmel, California. January 28- 31, 2010.

Rauen, K.A. 01-09-14

22

87. J Hogue, A Slavotinek, O Danhaive, M Wat, D Scott, Rauen KA. Chromosome 16p11.2 deletion: Expansion of the Phenotype to Include Diaphragmatic Hernia. Western Society of Pediatric Research Annual Meeting, Carmel, California. January 28- 31, 2010. 88. Bermudez-Wagner K, KK Drexler , A Mattis, P Ursell, KA Rauen. Trisomy 5 Mosciasm: Fetal effects of a rare chromosomal aberration. American College of Medical Genetics Annual Clinical Genetics Meeting, Albuquerque, NM, March 27-30, 2010. 89. Champion K, C Bunag, AL Estep, JR Jones, CH Bolt, C Rogers, KA Rauen, DB Everman. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. American College of Medical Genetics Annual Clinical Genetics Meeting, Albuquerque, NM, March 27-30, 2010. 90. Rauen KA, J McKenzie, IJ Frieden, DH Siegel. Dysregulation of Ras/MAPK Signaling in Epidermal Development: Dermatologic Findings in 61 Mutation Positive Individuals with CFC Syndrome. American College of Medical Genetics Annual Clinical Genetics Meeting, Albuquerque, NM, March 27-30, 2010. 91. J Hogue, A Slavotinek, O Danhaive, M Wat, D Scott, Rauen KA. Chromosome 16p11.2 deletion: Expansion of the Phenotype to Include Diaphragmatic Hernia. American College of Medical Genetics Annual Clinical Genetics Meeting, Albuquerque, NM, March 27-30, 2010. 92. Nowaczyk MJM, S Zeesman, KA Rauen. Deletion of MAP2K2: A possible novel mechanism for RASopathies? 31st Annual David W. Smith Workshop on Malformations and Morphogenesis, August 27 – September 1, 2010, Alderbrook Resort, Union, WA. 93. Klein, OD, A Goodwin , S Oberoi, C Charles, JC Groth, C Fairley, X Chen, J Fagin, KA Rauen. Biting into Costello syndrome: Ras signaling regulates enamel deposition in humans and mice. 60th Annual Meeting of American Society of Human Genetics, November 2-6, 2010, Washington, DC. Concurrent Platform Session 94. Sottile SL, A Kwan, P Magoulas, KA Rauen. Health-related quality of life in patients with cardio-facio-cutaneous syndrome (CFC). 11th Annual Clinical Genetics Exchange May 21, 2010, Stanford University, Palo Alto, CA. 95. Jelin AC, H Perry, J MacLean, B Shaffer, KA Rauen. Ellis-van Creveld and Neurofibromatosis: A Prenatal Dilemma. Western Society of Pediatric Research Annual Meeting, Carmel, California, January 26-28, 2011. 96. Wat MJ, D Veenma, J Hogue, AM Holder, Z Yu, J Wat, N Hanchard, OA Shchelochkov, CJ Fernandes, A Johnson, K P Lally, A Slavotinek, O Danhaive, T Schaible, S Cheung, KA Rauen, VS Tonk, D Tibboel, A de Klein, DA Scott. De novo and rare inherited genomic alterations provide insight into the genes responsible for isolated congenital diaphragmatic hernia and Pentalogy of Cantrell. 61th Annual Meeting of American Society of Human Genetics, October 11-15, 2011, Montreal, Canada. 97. Sottile SL, A Kwan, P Magoulas, KA Rauen. Health-related quality of life in patients with cardio-facio-cutaneous syndrome (CFC). 61th Annual Meeting of American Society of Human Genetics, October 11-15, 2011, Montreal, Canada. 98. Goodwin A, S Oberoi, C Charles, JC Groth, CF Fairley, X Chen, JA Fagin, KA Rauen, OD Klein. Gain-of-function in Ras signaling perturbs dental development in mouse and human. Society for Developmental Biology 69th Annual Meeting, August 5-9, 2010, Albuquerque, NM. 99. Oberoi S, Charles C, Goodwin A, Groth JC, Fairley CF, Rauen KA, and Klein OD. Characterizing the dental phenotype of Cardiofaciocutaneous syndrome. AADR General Session, March 16-18, 2011, San Diego, CA. 100. Rooney GE, LA Weiss, KA Rauen, EM Ullian. Investigating the role of Astrocytes in Plasticity and Disease. International Society for Stem Cell Research Annual Meeting, Toronto, 2011. 101. Stevenson DA, S Allen, WE Tidyman, JC Carey, DH Viskochil, A Stevens, H Hanson, X Sheng, BA Thompson, M Okumura, K Reinker, B Johnson, KA Rauen. Peripheral Muscle Weakness in RASopathies. Western Society of Pediatric Research Annual Meeting, Carmel, California, January 25-28, 2012 102. Goodwin A, S Oberoi, C Charles, JC Groth, CF Fairley, X Chen, JA Fagin, KA Rauen, Klein OD. Sinking our teeth into Costello syndrome: Ras signaling regulates enamel deposition in humans and mice. Gordon Conference on Craniofacial Morphogenesis & Tissue Regeneration, March 18-23, 2012, Ventura, CA.

Rauen, K.A. 01-09-14

23

103. Krencik R, GE Rooney, CM Schofield, LA Weiss, KA Rauen, EM Ullian,. Investigating the role of Astrocytes in Plasticity and Disease. Keystone Symposia on Molecular and Cellular Biology. Synapses and Circuits: From Formation to Disease, Colorado, 2012. 104. Thompson BA, M Nowaczyk, S Zeesman, U Moog, PA Sanchez-Lara, PL Magoulas, L Brueton, RE Falk, JH Fong, D Batista, S Manickavasagam-AMudhavalli, KA Rauen. MEK2 haploinsufficiency: A novel mechanism for a RASopathy. Clinical Genetics Exchange 13th Annual Meeting. May 2, 2012, Kaiser Permanente, Oakland, CA. 105. Krishnamurthi S, V Cox, KA Rauen. Neurofibromatosis Type 1 (NF1) and Infantile Myofibromatosis: A shared genetic basis or independently co-existent entities? Clinical Genetics Exchange 13th Annual Meeting. May 2, 2012, Kaiser Permanente, Oakland, CA. 106. Goodwin AF, S Oberoi, M Landan, C Charles, J Groth, A Martinez, C Fairley, LA Weiss, WE Tidyman, OD Klein, KA Rauen. Craniofacial and Dental Development in Cardio-facio-cutaneous Syndrome: The Importance of Ras Signaling Homeostasis. 62nd Annual Meeting of the American Society of Human Genetics, Moscone Center, San Francisco, CA. November 6-10, 2012. 107. Thompson BA, G Desachy, J Quinn, AE Toland, LA Weiss, KA Rauen. Single Nucleotide Polymorphisms (SNPs) and cancer risk in individuals with Costello Syndrome. 62nd Annual Meeting of the American Society of Human Genetics, Moscone Center, San Francisco, CA. November 6-10, 2012. 108. Corbin I, G Desachy, KA Rauen, LA Weiss. Autism Traits in the RASopathies. 62nd Annual Meeting of the American Society of Human Genetics, Moscone Center, San Francisco, CA. November 6-10, 2012. 109. Krishnamurthi S, V Cox, H Guo, KA Rauen. Neurofibromatosis Type 1 and Infantile Myofibromatosis. 62nd Annual Meeting of the American Society of Human Genetics, Moscone Center, San Francisco, CA. November 6-10, 2012. 110. Alvord BP, K A Rauen, A Stevens, H Hanson, X Sheng, DA Stevenson. Handedness in RASopathies. Western Society of Pediatric Research Annual Meeting, Carmel, California, January 24-26, 2013 (accepted). 111. Thompson BA, G Desachy, AE Toland, LA Weiss, KA Rauen. Single Nucleotide Polymorphisms (SNPs) and cancer risk in individuals with Costello Syndrome. Clinical Genetics Exchange 14th Annual Meeting. May 17, 2013, Children’s Hospital Oakland and Research Institute, Oakland, CA. 112. Messiaen LM, J Xie, AB Poplawski, YF Liu, A Gomes, P Madanecki, C Fu, MR Crowley, D Crossman, L Armstrong, D Babovic-Vuksanovic, A Bergner, JO Blakeley, AL Bloomingthal, M Daniels, H Feit, K Gardner, S Hurst, C Kobelka, R Nagy, KA Rauen, J Slopis, P Suwannarat, J Westman, BR. Korf, A Piotrowski. Germline loss-of-function mutations in LZTR1 cause an inherited disorder of multiple schwannomas in SMARCB1-negative patients. 63rd Annual Meeting of the American Society of Human Genetics, Boston, MA. October 22-26, 2013. RESEARCH PROGRAM Five Significant Publications: 1) Tartaglia M, PD Cotter, G Zampino, BD Gelb and KA Rauen. 2003. Exclusion of PTPN11 mutations in Costello syndrome: Further evidence for distinct genetic etiologies for Noonan, cardio-facio-cutaneous and Costello syndromes. Clinical Genetics 63: 423-426. I was the senior and corresponding author on this project and proposed the hypothesis that Costello syndrome was due to perturbation of the Ras/MAPK pathway leading to a subsequent body of work that resulted in the CS and CFC gene discoveries. In addition, this hypothesis was the basis for my K-grant which was successfully funded. As it turned out, CS was due to activating HRAS mutation which I independently identified. 2) Estep AL, WE Tidyman, MA Teitell, PD Cotter, KA Rauen. 2006. HRAS Mutations in Costello Syndrome: Detection of Constitutional Activating Mutations in Codon 12 and 13 and Loss of Wild-type Allele in Malignancy. American Journal of Medical Genetics Jan 1;140(1):8-16. I was the senior and corresponding author on this project. My lab independently identified HRAS mutations in CS and proposed the hypothesis that CFC syndrome was genetically distinct from Costello syndrome and was also due to perturbation of the Ras/MAPK pathway. In addition, I was the first

Rauen, K.A. 01-09-14

24

to demonstrate that malignancies for CS individuals have loss of heterozygosity of HRAS. This project provided further ground work for the CFC gene discovery in my lab. 3) Rodriguez-Viciana P, O Tetsu, AL Estep, WE Tidyman, BA Conger, M Santa Cruz, F McCormick, KA Rauen. 2006. Germline mutations in genes within the MAPK cascade cause cardio-facio-cutaneous syndrome. Science. 311(5765):1287-90. I was the senior and corresponding author on this project and proposed the candidate genes to sequence based on previous work I had done on this syndrome in my lab. This study also determined the first human genetic evidence for the linear nature of the MAPK pathway downstream of Ras and also identified the first reported mutations (germline or somatic) in MEK genes. Identifying mutations in MEK directed my lab and then other labs to identify and subsequently publish somatic mutations in MEK in ovarian, lung cancer and melanoma. 4) Rauen KA. Distinguishing Costello vs Cardio-facio-cutaneous Syndrome: BRAF Mutations in Patients with a Costello Phenotype. 2006. American Journal of Medical Genetics. 140A:1681-1683 This was a landmark study and the first providing molecular evidence that phenotypically similar syndromes have heterogeneous gene mutations affecting the same signal transduction pathway, further defining the linear nature of the Ras/MAPK pathway in human genetics and development. 5) Rauen KA, et al. Proceedings from the 2009 Genetic Syndromes of the Ras/MAPK Pathway: From bedside to bench and back. 2010. American Journal of Medical Genetics. A 152A:4–24. This work represents the culmination of work I have done over the last 11 years on the “RASopathies” (a term that I coined which is now used internationally) — the group of genetic syndromes caused by germline dysregulation of the Ras/MAPK pathway. This symposium, which I organized and chaired, brought together international experts in the field of the Ras/MAPK Pathway and provided the framework and established the groundwork onto which the discussions for clinical trials in Noonan, Costello and CFC syndromes will move forward. My insistence for this meeting that the syndrome advocacy groups come together was unprecedented for NS, NF1, CS and CFC organizations and truly set the stage for all the RASopathy meetings that have followed. This International meeting was followed-up by a workshop that I sponsored by a UCSF CTSI grant which set forth the paradigm for clinical trials for CS and CFC. The workshop was published: Rauen KA et al, Costello and cardio-facio-cutaneous syndromes: Moving toward clinical trials in RASopathies. American Journal of Medical Genetics. 157(2):136-46. 2012. RASopathy Clinic and Translational Program: The RASopathy clinical translation program, the first of its kind, bridges pediatric and adult disciplines, as well as unites the School of Medicine, the Medical Center and the UCSF Helen Diller Family Comprehensive Cancer Center. My ultimate goal is to create the first Center Of Excellence for RASopathies.

1) Research Program:

A class of medical genetic syndromes has emerged caused by germline mutations in genes associated with the Ras/mitogen-activated protein kinase (MAPK) pathway, which I have termed “RASopathies”. My research program involves the clinical, translational and basic science study of these cancer syndromes with efforts to identify underlying genetic abnormalities affecting common developmental and cancer pathways. I mainly focus on two RASopathies within this pathway: Costello syndrome (CS) and cardio-facio-cutaneous syndrome (CFC). CS is a complex developmental disorder involving characteristic craniofacial features, failure to thrive, developmental delay, cardiac and skeletal anomalies, hypotonia and a predisposition to develop neoplasia, both benign and malignant. CS is caused by activating germline mutations in HRAS which we independently identified in my lab. Like CS, CFC is also a rare multiple congenital anomaly disorder caused by germline mutations identified by my lab: BRAF, MEK1 and MEK2 within the MAPK pathway, one of the downstream cascade effected by Ras. The type of BRAF

Rauen, K.A. 01-09-14

25

mutations found in CFC recapitulates the different types of mutations found in cancer which cause an alteration of signaling in the MAPK cascade. However, in contrast to the mutation spectrum seen in cancer, the majority of BRAF mutations we identified in CFC are novel. Understanding the genetic role of HRAS in CS and BRAF, MEK1 and MEK2 in CFC syndrome is the first step in gaining insight to the role Ras plays in human development including skeletal myogenesis, cellular signaling and cancer progression. The overall goal of this work is to move towards treatment for this group of syndromes. Along with understanding the basic biochemical alteration of germline mutation in BRAF and MEK in my lab, we most recently defined a novel myopathy in patients with CS and CFC syndrome. This work culminated in robust preliminary data to secure extramural funding via an NIH/NIAMS R01 grant. There are numerous intracellular signaling pathways, including the Ras pathway, involved in normal muscle development. My R01 proposes experiments addressing the cellular mechanisms that mediate myogenesis and its dysregulation using mouse models for CS and CFC. The results of these studies should provide new insight into the mechanisms of muscle development and disease, and ultimately rhabdomyosarcoma, as well as reveal new targets for therapeutic intervention. 2) Clinic Program: UCSF NF/Ras Pathway Genetics Clinic

In 2007, I created a new UCSF clinic and developed a new clinical model for individuals who have been diagnosed with RASopathies or suspected of having a RASopathy. The pathway-based clinic has been exceptionally successful here at UCSF and has served as a template by other Medical Centers in the country and around the world. We have a large catchment with patients coming as far away as Venezuela, Singapore and Hawaii. Although individually rare, this group of genetic syndromes together represents one of the largest classes of Mendelian genetic disorders. Their common underlying pathogenetic mechanism brings about significant overlap in phenotypic features resulting in common specialty care needs which inspired the concept of a pathway-based (instead of a disease-based) clinic. The clinic’s unique attributes include: 1) a pathway-based approach; 2) life-long, comprehensive case management and multidisciplinary referrals within one provider network; 3) a network of more than 60 UCSF specialists at a single tertiary care center; 4) facilitated transition from pediatric to adult care in all specialties; 5) pre-implantation, prenatal and obstetric care; 6) guidance from an external patient advocacy advisory board and 7) guidance from an internal scientific advisory board. We are working toward becoming a center for Ras translational medicine, a training venue for translational research and a hub for clinical trials. This novel clinic is a model not only for the care of individuals with Ras pathway disorders, but also for other groups of rare, but overlapping genetic disorders.

The clinical translational research program which stems from the Ras Clinic now has several core faculty (Laurie Weiss, Ophir Klein, Erik Ullian), all collaborating in research endeavors. We have established a large RASopathy biobank (in collaboration with Dr. Weiss) of DNA samples and other specimens including urine, saliva and various miscellaneous tissue samples. These samples are linked to clinical data. We have produced numerous lymphoblastoid cell lines, as well as fibroblast cells lines and have created iPSCs for basic research and clinical translational studies. This is a collaborative effort of UCSF PIs dedicated to RASopathy research and who have joined together to help establish this RASopathy research group.

Documents

University of California, Davis CURRICULUM VITAE Name ... · 2010-pres Editor, Genetics in Medicine (Journal - Am College of Med Genetics and Genomics) Invited Presentations 1991