8th Annual Postdoctoral

Science Symposium

October 2, 2018

Organized by the MD Anderson Postdoctoral Association Sponsored by The University of Texas MD Anderson Cancer Center Office of Postdoctoral Affairs and Development, a unit of the division of Education and Training

October 2, 2018Morning Sessions9:00 am

Opening and IntroductionsAPSS Organizing Committee and PDAEC Chair

9:10 – 10:00 am

Applied Science Oral Presentations

Bhasker Radaram, Ph.D.Department of Cancer Systems ImagingMD Anderson Cancer Center“Conjugation of HOPO to protein and radiolabeling with Zr-89: comparative stability and biodistribution in normal mice”

Natalia Heredia, Ph.D.Department of Health Disparities ResearchMD Anderson Cancer Center“Co-action between physical activity and fruit and vegetable intake in a racially diverse group of obese adults”

David Frank, Ph.D.Department of Behavioral ScienceMD Anderson Cancer Center“Identifying smokers at higher risk for relapse: Validation of a neuroimaging-based classification algorithm”

Jemima John, Ph.D.Department of Health Disparities ResearchMD Anderson Cancer Center“A process evaluation of satisfaction and engagement measures from Project FITT: A mixed methods study ”

10:00 – 11:00 am

Invited Speaker

Alessandro Grattoni, Ph.D.Associate Professor, Research Institute ChairDepartment of NanomedicineHouston Methodist

“Micro-Nanotechnologies for medicine on-Earth and in Space”

Symposium Agenda

11:10 - 11:40 am

Poster Session 1 / Coffee Break

11:40 – 12:30 pm

Basic Research Oral Presentations

Prosun Das, Ph.D.Department of Epigenetics and Molecular Carcinogenesis,MD Anderson Cancer Center“Histone Methylation Regulator PTIP is Required to Maintain Normal and Leukemic Bone Marrow Niches”

Maria Neus Bota Rabassedas, Ph.D.Department of Thoracic Head and Neck Medical Oncology

MD Anderson Cancer Center“Metastatic tumor cells influence the transcriptomic and positional heterogeneity of cancer-associated fibroblasts”

Emilly Schlee Villodre, Ph.D.Department of Breast Medical OncologyMD Anderson Cancer Center“Lipocalin 2 promotes inflammatory breast cancer tumorigenesis and skin invasion”

Jia Li, Ph.D.Center for Epigenetics & Disease PreventionInstitute of Biosciences and TechnologyTexas A&M Health Science Center College of Medicine“Tet protein mediated DNA methylation oxidation regulates ventricular chamber development”

12:30 – 1:30 pm

Breakout Sessions / Lunch

WORKSHOP: How to NegotiateMain Building R11.1100 Ballrooms 7 & 8

Grants: Navigating the Process Pre- and Post-AwardMain Building R11.1100 Ballrooms 5 & 6

Symposium Agenda

Afternoon Sessions

1:30 – 2:30 pm

Invited Speaker

Ilya Levental, Ph.D.Assistant Professor, CPRIT ScholarDepartment of Integrative Biology and PharmacologyUTHealth

"The organization and function of the mammalian plasma

membrane"

2:30 – 3:20 pm

Clinical/Translational Research Oral Presentations

Jeremy Schraw, Ph.D.Department of MedicineBaylor College of Medicine“Metabolomic profiling improves prediction of minimal residual disease and reveals potential metabolic vulnerabilities in pediatric acute lymphoblastic leukemia”

Vaishnavi Sambandam, Ph.D.Department of Thoracic Head and Neck Medical OncologyMD Anderson Cancer Center“Susceptibility of NOTCH1 mutant head and neck squamous carcinoma to PI3K/mTOR pathway inhibition via PDK1”

Nicole Kettner, Ph.D.Department of Experimental Radiation OncologyMD Anderson Cancer Center“Combined inhibition of STAT-3 and DNA repair in palbociclib resistant ER-positive breast cancer cells”

Vancheswaran Gopalakrishnan, Ph.D.Department of Surgical OncologyMD Anderson Cancer Center“Implications for clinical trial design based on host factors and variation of the gut microbiome of complete responders to immune checkpoint blockade and healthy individuals ”

Symposium Agenda

3:20 – 4:00 pm

Poster Session 2 / Coffee Break

4:00 – 5:00 pm

Keynote Presentation

Michelle C. Barton, Ph.D.Professor and Dean of GSBSDepartment of Epigenetics and Molecular CarcinogenesisMD Anderson Cancer Center

"Following the last refuge of scoundrels all the way to therapeutic potential"

5:00 – 5:15

Award Ceremony and Closing Remarks

5:15 – 6:15 pm

Reception

Symposium Agenda

Distinguished Speakers

Professor and Dean of GSBSDepartment of Epigenetics and Molecular Carcinogenesis

UT MD Anderson Cancer Center

Michelle C. Barton Ph.D.Keynote Speaker

Education: Degree-Granting Education1978 B.S. Biochemistry University of Illinois, Urbana-Champaign 1989 Ph.D. Biochemistry University of Illinois, Urbana-Champaign

Research InterestDr. Barton’s research expertise is in chromatinbiology and epigenetic regulators, which shehas applied in her focus on the roles of p53 instem cells, cancers and regenerating liver.More recently, her laboratory identified apreviously unknown negative regulator of p53,TRIM24. Dr. Barton collaborated with the MDAnderson Cancer Center Institute of AppliedCancer Science in the development ofepigenetic-based therapeutic agents thattarget specific domains of epigeneticregulators, which are aberrantly expressedand/or mutated in human cancers. Recently,the Barton lab defined and annotated a set ofp53-regulated lncRNAs that impact stem cellpluripotency or differentiation. Activecollaborations with pathologists, clinical andsurgical oncologists are laying the groundworkfor translation of these mechanistic findings.

Postgraduate Training1989-1994 Postdoctoral Fellow The Salk Institute, La Jolla, CA

Notable Honors/Awards2003- John P. McGovern Outstanding Teacher Award2008- MD Anderson Faculty Achievement Award in Education2009- Robert M. Chamberlain Distinguished Mentor Award2011-2016- Ashbel Smith Professor Endowed Position, MD Anderson2011 Paul E. Darlington Mentor Award2015- Fellow, American Association for the Advancement of Science2016- Colin Powell Endowed Chair for Cancer Research2016- Texas Business Women’s Award, Houston, TX2017- BioHouston Women in Science with Excellence (WISE) Award2017- The R. Lee Clark Prize, President’s Recognition for Faculty Excellence2018- President’s Recognition of Faculty Excellence in Education and Mentoring Advancement

Professor and Research Institute ChairDepartment of Nanomedicine

Houston Methodist

Alessandro Grattoni, Ph.D.

Invited Speaker

Education:

B.S. Mechanical Engineering - Polytechnic of Turin, ItalyM.S Mechanical Engineering - Polytechnic of Turin, ItalyPh.D. Biomedical Engineering - Polytechnic of Turin, Italy / research performed at the Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston.

BioDr. Grattoni completed his M.S. in mechanical engineering studying osmoticpressure of non-electrolytes solutions. He enrolled in a Ph.D. program inbiomedical engineering, and Joined Dr. Mauro Ferrari’s team at UTHSC atHouston. Here he focused on the study of nanochannel silicon membranesfor drug delivery. After completing his Ph.D. degree in 3 years, and one yearof postdoctoral fellowship, in 2010 Dr. Grattoni joined the HoustonMethodist Research Insititute (HMRI) as an assistant professor. He iscurrently the Chair and Professor in Department of Nanomedicine at HMRI.His research is dedicated to the development and translation of implantablenanofluidic platforms for controlled drug delivery and cell transplantation.These include systems for HIV PrEP, obesity and metabolic syndrome, andintratumoral cancer immunotherapy. He has also engaged in the analysis ofelectrokinetics for remotely controlled drug delivery for telemedicine andpersonalized therapeutics. His team is developing a 3D-printedencapsulation device, the NICHE, for endocrine cell transplantation. Dr.Grattoni established the Center for Space Nanomedicine at HMRI, dedicatedto leveraging the International Space Station for the investigation ofnanotechnologies for applications on-Earth and in Space. Dr. Grattoni hasreceived support from, NIH, CASIS, NASA, DOD, JDRF, Gilead Sciences,Lamborghini, and numerous foundations.

Assistant Professor, CPRIT ScholarDepartment of Integrative Biology and Pharmacology

UTHealth

Ilya Levental, Ph.D.

Invited Speaker

Education: Degree-Granting EducationGeorgia Institute of Technology B.S. Chemical Engineering 06/03

University of PennsylvaniaPh.D. Bioengineering 06/08

BioI began my career as an engineer, earning a BS in Chemical Engineering atGeorgia Tech, while doing two years of undergraduate research onnanobiotechnology. My excitement about the intersection of engineeringand biology led me to a PhD in Bioengineering from the University ofPennsylvania, where my interest in the molecular mechanisms andbiological role of membrane structure developed. I independentlyconceived an idea for my postdoc research, which led to a prestigiouspostdoctoral funding grant through the Humboldt Foundation in Germany,with the research being conducted in Dr. Kai Simons’ lab at the Max PlanckInstitute of Molecular Cell Biology and Genetics. In 2012, I was hired as anAsst Prof in the Integrative Biology and Pharmacology department atUTHealth, where I use classical cell biology, biophysics, synthetic biologyand computational modeling to characterize the role of membranestructure in the regulation of cell function. The ultimate goal of my researchis to understand how the complex membrane matrix that hosts thefunction of thousands of proteins regulates cell physiology and dysfunction.

Postgraduate TrainingMax Planck Institute of Cell Biology and GeneticsPostdoctoral - Cell Biology 06/12

Oral Speakers

Research Interest:My research interests include the design, synthesis and development of radiotracers such aschelators for radioactive metals, small biologically active molecules for Molecular Imagingespecially non-invasive PET Imaging probes for early detection of various cancers. Furtherinvestigation of biological activity of radiotracers both in in vitro and in vivo.

Abstract:Conjugation of HOPO to protein and radiolabeling with Zr-89: comparative stability andbiodistribution in normal miceBhasker Radaram1, Sandun Perera2, David Piwnica-Worms3, Mian M Alauddin4

1Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department ofCancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Cancer SystemsImaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Cancer Systems Imaging, TheUniversity of Texas MD Anderson Cancer Center, Houston, TX

Objectives: Zirconium-89 is attractive for use in antibody-based PET imaging due to itsradiodecay half-life compatible with the biological half-life of antibodies. Deferoxamine (DFO)has been commonly used as a chelating agent for this purpose.1 However, DFO-chelated 89Zrcan suffer from in vivo stability challenges.2 A new chelating agent, 3,4,3-(LI-1,2-HOPO) (HOPO),has demonstrated efficient binding of 89Zr with high stability.3 We have synthesized threeanalogues of HOPO that show higher in vitro and in vivo stability with 89Zr. We presentconjugation of HOPO to protein, radiolabeling with 89Zr, stability of the labeled proteinconjugates and their biodistribution results. Methods: Chemistry: Figure 1 represents thescheme for synthesis of one ligand. Briefly, N-protected amino-alkyl iodide was reacted withspermine. The mono-substituted spermine derivative was reacted with HOPO acid chloride toget substituted spermine-HOPO derivative. The amino protecting group from the spermine-HOPO derivative was hydrolysed by acid and the amino-alkyl-spermine-HOPO reacted withphenylene-di-isothiocyanate to obtain p-SCN-phenyl-alkyl-spermine-HOPO.Conjugation and radiolabeling: p-SCN-phenyl-C5-spermine-HOPO, was conjugated with humanor bovine serum albumin, purified and the conjugated proteins were radiolabeled with 89Zr-oxalate. After purification on a PD-10 column, the products were tested for in vitro stability andbiodistribution.Animal study: Two groups of healthy athymic nude mice (n=4 per group) wereinjected (intravenous) with 89Zr-HOPO-BSA or 89Zr-DFO-BSA (12-20 μCi) in PBS. Mice werescanned every 24 h up to 48 h for PET Imaging. After imaging, all mice were sacrificed andorgans, including blood, muscle, bone, heart, lung, liver, spleen, pancreas, intestine, stomach,and kidney were isolated, weighed and radioactivity counted on a gamma counter.Radioactivity accumulation was expressed as percent injected dose/gram and averaged withstandard deviation.Results: HOPO analogues were synthesized in 4 steps with an overall yieldof 10%. Stability of 89Zr-HOPO-albumin in both human serum and mouse serum and at differentpH (5, 6, 7, 8) remains intact and shows better stability compared to 89Zr-DFO-albumin.Preliminary biodistribution of 89Zr-HOPO-protein in normal mice indicates good stability andshows more uptake in liver, spleen and kidney.Conclusion: Radiolabeling of protein with 89Zrusing of p-SCN-phenyl-alkyl-spermine-HOPO with different carbon chain lengths has beenachieved. In vitro and in vivo stability suggest that that 89Zr-labeled protein using HOPO aschelating agent is more stable than DFO-conjugated products. Further in vivo studies with 89Zr-DFO-mAb and 89Zr-HOPO-mAb are in progress for comparison.

Email: bradaram@mdanderson.org

Bhasker Radaram, Ph.D. Department of Cancer Systems ImagingMD Anderson Cancer Center

Mentors: Dr. Mian Alauddin, Dr. David Piwnica-Worms

Research Interest:Hispanic health disparities, physical activity, nutrition, obesity, non-alcoholic fatty liver disease

Abstract:Co-action between physical activity and fruit and vegetable intake in a racially diverse groupof obese adultsNatalia Heredia1, Maria Fernandez2, Alexandra van den Berg2, Casey Durand2, Harold Kohl III2,Belinda Reininger2, Kevin Hwang3, Lorna McNeill11The University of Texas MD Anderson Cancer Center, 2The University of Texas Health Science Center at Houston, School ofPublic Health, 3McGovern Medical School at the University of Texas Health Science Center at Houston

Background. Despite inclusion of both physical activity and fruit and vegetable intake as targetbehaviors in multiple-behavior change weight management programs, there is minimalunderstanding of co-action, or change in one behavior influencing change in the other. Co-action between self-efficacy for physical activity and self-efficacy for fruit and vegetable intakeis also possible, though there is little research in this area. The purpose of this study is to assessthe bi-directional co-action between fruit and vegetable intake and physical activity, as well asself-efficacy for fruit and vegetable intake and physical activity, in a racially diverse sample ofobese adults in Houston.Methods. This was a secondary data analysis of a randomized controlled trial designed tonavigate obese adults to commercially-available weight management programs. At baseline, 3and 6 months, participants completed the NCI/NIH fruit and vegetable screener, the GodinLeisure-Time Exercise Questionnaire, and self-efficacy for physical activity and fruit andvegetable intake questions and wore an accelerometer for seven days. We generatedcontinuous change scores and categorized the change score into negative change, no change,or positive change. We conducted multiple imputation and both linear and multinomialregression, adjusting for covariates, using Stata/SE 14.2.Results. The sample (n=168) was primarily female (59%), married or living with a partner (53%),and mostly white (42%) or African American (42%). In linear regression analyses, positivechange in self-efficacy for physical activity was predictive of positive change in self-efficacy forfruit and vegetable intake (Adjusted B=0.20, 95%CI 0.05-0.35), and positive change in self-efficacy for fruit and vegetable intake was predictive of positive change in self-efficacy forphysical activity (Adjusted B=0.25, 95%CI 0.05-0.45). In multinomial logistic regression, ascompared to no change, someone with a positive change in fruit and vegetable intake wasmore likely to have a positive change in self-reported physical activity (Adjusted RR=6.72, 95%CI 1.69-26.68). Likewise, as compared to no change, someone with a positive change in self-reported physical activity was more likely to have a positive change in fruit and vegetableintake (Adjusted RR=6.79, 95% CI 1.70-27.17).Conclusion. Findings suggest co-action between self-efficacy for fruit and vegetable intake andphysical activity, as well as between fruit and vegetable intake and physical activity. Co-actioncould be capitalized on within the course of an intervention to efficiently and effectivelyimprove both cancer prevention behaviors.

Email: niheredia@mdanderson.org

Natalia Heredia, Ph.D. Department of Health Disparities ResearchMD Anderson Cancer Center

Mentor: Dr. Lorna McNeill

Research Interest:My research interests pertain to neural biomarkers for addiction and compulsive behavior,particularly related to tobacco use and excessive food consumption.

Abstract:Identifying smokers at higher risk for relapse: Validation of a neuroimaging-basedclassification algorithm

David W. Frank1, Menton E. Deweese1, Maher Karam-Hage1, Jason D. Robinson1, Damon J.Vidrine2, Paul M. Cinciripini1, Francesco Versace1

1UT MD Anderson Cancer Center, 2University of Oklahoma Tobacco Research Center

Progress in basic neuroscience has improved our understanding of addiction neurobiology, butwhat has proven difficult is translating this knowledge into effective relapse preventiontreatments (Everitt, 2014). Recently, we reported that smokers with larger event-relatedpotentials (ERPs; a direct measure of brain activity) to cigarette-related cues compared topleasant stimuli (“C>P”) are more likely to relapse than smokers with the opposite brainreactivity profile (“P>C”). We hypothesized that this neurobiological marker could be used toidentify smokers with high vulnerability to relapse. In this study, we aimed to 1) build aclassification algorithm to identify, on a case by case basis, smokers characterized by the P>C orthe C>P ERP profiles, and 2) validate the clinical relevance of this classification algorithm in anindependent dataset where we assessed smoking abstinence during a quit attempt in smokersclassified as P>C or C>P. To build the classification algorithm, we applied discriminant functionanalysis on a dataset where we originally observed a significant association between smokingabstinence and neural reactivity to emotional stimuli. We confirmed the predictive validity ofthe classification algorithm on an independent data set that included new data from 177smokers interested in quitting. For each participant we collected ERPs to emotional imagesbefore the quit attempt and we assessed smoking abstinence 12 months after the quit attempt.Using brain responses, the algorithm classified 111 smokers as P>C and 66 as C>P. The overalllow abstinence rate notwithstanding (8.5% of the sample achieved CO verified 12 monthsabstinence), individuals classified as P>C were 2.5 times more likely to be abstinent thansmokers classified as C>P (12% vs. 4.8%). Although this difference did not reach statisticalsignificance (p=.08), these results suggest that neuroimaging techniques can help advance ourknowledge of the neurobiological underpinnings of nicotine addiction and improve clinicalapplications.

Email: dfrank@mdanderson.org

Department of Behavioral ScienceMD Anderson Cancer Center

Mentor: Dr. Francesco Versace

David Frank, Ph.D.

Research Interest:Dr. John’s research focuses on the influences of social support, social control and partner relationships onphysical activity (PA), related health behaviors, and cancer risk reduction in underserved populations, such asHispanic and African American Populations.

Abstract:A process evaluation of satisfaction and engagement measures from Project FITT: A mixedmethods studyJohn JC1, Wang J2, McNeill LM3, Basen-Engquist K4, Daniel-MacDougall CR5, Strong LL6

11The University of Texas MD Anderson Cancer Center, 21The University of Texas MD Anderson Cancer Center, 31TheUniversity of Texas MD Anderson Cancer Center, 41The University of Texas MD Anderson Cancer Center, 51The University ofTexas MD Anderson Cancer Center, 61The University of Texas MD Anderson Cancer Center

Background & Purpose: Physical activity (PA) guards against many chronic morbidities. However,over two-thirds of U.S. adults are insufficiently active, with Black and Latino populations reportinglower rates of PA than non-Latino White Americans. Thus, a 16 week pilot intervention wasconducted to promote moderate to vigorous PA among sedentary African-American and Latinowomen. The study enrolled dyads (family, friends, co-workers) and digital delivered interventioncomponents to facilitate social interactions and social support for increased PA. Given that this was apilot study, it was important to assess receptiveness to intervention components to build on existingknowledge and improve the implementation process of future studies. The purpose of this paper wastwofold: 1) quantitatively and qualitatively examine participants’ engagement and satisfaction withthe intervention and, 2) assess relationships between PA measures and PA outcomes at week 8 andweek 16.Methods: A mixed-methods approach was used to evaluate the data of 16 dyads who wereassigned to the intervention, which included 1) six dyad-based telephone counseling calls, 2) aJawbone activity tracker which featured a built-in social network app, and 3) electronic healthnewsletters. PA data and, satisfaction and engagement metrics were collected via self-reportedsurveys, the Jawbone device and accelerometers. We used both parametric and non-parametric teststo examine the presence of significant associations at p-value <0.05. Qualitative data were collectedin post-intervention focus groups to identify significant themes in participants’ experiences andsatisfaction with the intervention. Results: 46% of dyads were family members, 53% of participantswere Black, and mean age and BMI were 43.7 years and 35.6 kg/m2 respectively. Interventionengagement was high; 92% of participants completed the six counseling calls and participants worethe Jawbone 88% of days during the first month. However, Jawbone usage declined over time, withparticipants wearing the device only 56% of days during the last month. Jawbone usage (% days)differed significantly across partner type and age category, with co-worker dyads and the >45 yearsage group using the jawbone more (p<0.05). Results also showed that 85% of Latino womencompared to 37.5% of Black women believed that study newsletters led to an increase in PA levels(p<0.05). Lastly, Jawbone steps was positively associated with moderate-vigorous PA at week 8(p<0.05) but not at week 16. Both qualitative and quantitative data showed that participants widelyliked the Jawbone device. However, some participants described frustration and discomfort with thedevice, which led them to stop using it. Qualitative findings showed that participants stronglyappreciated the intervention’s dyad structure and use of phone counseling sessions- both of whichfacilitated social support and accountability throughout the study. Conclusion: Our qualitative andquantitative findings highlighted participants’ preference for studies that encourage interaction,social support, and accountability. Our findings also indicate that qualitative data are equallyvaluable and can provide enhanced meaning to quantitative results. Furthermore, this study showedthat smart phone technology is effective in reaching and engaging with minority populations, andsuch devices must be promoted in PA behavioral intervention design and delivery.

Email: jcjohn@mdanderson.org

Jemima John, Ph.D. Department of Health Disparities ResearchMD Anderson Cancer Center

Mentor: Dr. Larkin Strong

Research Interest:The project identifies the histone methylation regulator PTIP directly regulates the expressionof PPAR-gamma, a transcription factor that is essential for osteoclastogenesis. Our dataindicate that PTIP is required for the integrity of of the bone marrow niche to sustain bothnormal hematopoiesis and leukemia.

Abstract:Histone Methylation Regulator PTIP is Required to Maintain Normal and Leukemic BoneMarrow Niches

Prosun Das1, Kylee Veazey1, Hieu Van1, Saakshi Kaushik1, Masaru Ishii2, Junichi Kikuta2, Kai Ge3,Andre Nussenzweig4, Margarida Almeida Santos1,5

1Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD AndersonCancer Center, Houston, TX 77030, USA, 2Department of Immunology and Cell Biology,Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka 565-0871,Japan, 3Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes andDigestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA, 4Laboratory of GenomeIntegrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA, 5Center for CancerEpigenetics, MD Anderson Cancer Center, Houston TX 77030, USA

The bone constantly undergoes a dynamic process of remodeling in which osteoblasts areresponsible for bone formation and osteoclasts for its resorption. This remodeling process isclosely associated with the maintenance of the endosteal bone marrow (BM) niche, located atthe interface of the bone and BM, and is essential for hematopoietic stem cells (HSC)occupancy within the niche. Although the cellular components of the BM endosteal niche havebeen characterized, little is known about its epigenetic regulation. Here we find that theMLL3/4 histone methyltransferase complex subunit PTIP (Pax interaction with transcription-activation domain protein-1) is required to maintain the integrity of the HSC niche bypromoting osteoclast differentiation. PTIP directly promotes chromatin changes required forthe expression of PPARγ (Peroxisome proliferator-activated receptor gamma), previouslyshown to be essential for osteoclastogenesis. We show that the deletion of PTIP in mousehematopoietic progenitor cells disrupts the BM endosteal microenvironment byblocking PPARγ-mediated osteoclast differentiation. This leads to an increase in bone volumeand results in a decrease in medullary cavity space, consequently inducing extramedullaryhematopoiesis and a drastic reduction of the HSC pool with in the BM compartment.Furthermore, the exposure of acute myeloid leukemic (AML) cells to a PTIP-deficient BMmicroenvironment leads to a reduction in leukemia initiating cells (LICs) in the BM, negativelyimpacting their functionality and hence positively affecting survival upon transplantation. Thus,in addition to establishing a novel role for PTIP in the integrity of the endosteal BM niche, thesedata constitute an important contribution to the concept of BM microenvironment modulationas a strategy to reduce LICs and a potential therapeutic scheme to relieve leukemia

Email: pdas@mdanderson.org

Prosun Das, Ph.D. Department of Epigenetics and Molecular Carcinogenesis

Mentor: Dr. Margarida Almeida Santos

Research Interest: My research focuses on lung cancer microenvironment. Specifically, I amstudying the role cancer associated fibroblasts (CAFs) play in early metastasis. For this purpose,I am studying CAFs heterogeneity, both within and at the periphery of the tumor, to elucidatethe distinct subpopulations. Moreover, we are also studying the interaction between CAFs andfunctionally different tumor cells, to elucidate the nature between said interactions.

Abstract:Metastatic tumor cells influence the transcriptomic and positional heterogeneity of cancer-associated fibroblastsMaria Neus Bota Rabassedas1, Priyam Banerjee1, Kuanwei Sheng2, Jacob Albritton3, Yuanxin Xi1,Michael Weiger1, Xin Liu1, Xiaochao Tan1, Hou-Fu Guo1, Jiang Yu1, Jaime Rodriguez1, BarbaraMino1, Chad Creighton2, Luisa Solis1, Pamela Villalobos1, Dan Sazer3, Nick Calafat3, DonGibbons1, Ignacio Wistuba1, Jing Wang1, Jordan Miller3, Chenghang Zong2, Jonathan Kurie1

1UT MD Anderson Cancer Center, 2Baylor College of Medicine, 3Rice University

It has become increasing clear that metastasis is driven by complex cell-cell interactions. Withinthe tumor stroma, cancer-associated fibroblasts (CAFs) localize in a non-uniform pattern, whichis indicative of CAF heterogeneity, but the underlying basis of CAF heterogeneity and the way inwhich CAF subpopulations promote metastasis remain unclear. To address these questions, weperformed single cell RNA sequencing on CAFs isolated from mice that develop lungadenocarcinoma owing to expression of a KRASG12D allele, which revealed 4 CAF subpopulationsthat, by gene set enrichment analysis, exhibited distinct pro-metastatic properties, includingcell migration, epithelial-to-mesenchymal transition, and extracellular matrix production.Expression signatures from 2 CAF subpopulations had poor-prognostic value in human lungadenocarcinoma cohorts. On the basis of these findings, we hypothesized that a highly motileCAF subpopulation enhances the metastatic capacity of lung adenocarcinomas. To test thishypothesis, we created aggregates of murine CAFs and highly or poorly metastatic lungadenocarcinoma cells and subjected the aggregates to live-cell imaging in 3-dimensionalcollagen matrices. In the highly metastatic KP cell aggregates, CAFs migrated rapidly to theaggregate periphery and positioned themselves at the tips of tumor cells that collectivelyinvaded into the collagen matrix. Invasive projections were more numerous in CAF-containingaggregates than they were in those lacking CAFs. However, in the poorly metastatic tumor cellaggregates, CAFs did not migrate to the periphery or increase the numbers of invasiveprojections. Similar differences in CAF localization patterns and invasive activities wereobserved following co-injection of CAFs and highly or poorly metastatic tumor cells intosyngeneic, immunocompetent mice. Because the highly metastatic tumor cells exhibit a uniquecapacity to undergo epithelial-to-mesenchymal transition (EMT), we reasoned that tumor cellEMT may regulate CAF migratory properties. Through genetic manipulation of tumor cells, wefound that EMT triggered CAF migration to the aggregate periphery by inducing contactinhibition of locomotion (CIL), a mechanism by which cell migratory direction changes uponcontact with another cell. These findings demonstrate that CAF subpopulations differ withrespect to pro-metastatic properties and that CAF motility drives metastasis and is regulated bytumor cell EMT.

Email: mbota@mdanderson.org

Maria NeusBota Rabassedas, Ph.D. Thoracic Head and Neck Medical OncologyMD Anderson Cancer Center

Mentor: Dr. Jonathan Kurie

Research Interest:My research interest is to determine the function of the protein Lipocalin 2 (LCN2) in thetumorigenesis of inflammatory breast cancer (IBC) and to comprehend the mechanism of tumorprogression and metastasis.Abstract:Lipocalin 2 promotes inflammatory breast cancer tumorigenesis and skin invasionEmilly Schlee Villodre1,10, Richard Larson2,10, Xiaoding Hu1,10, Shane R Stecklein2,10, Kristen Gomez6,Pascal Finetti8, Savitri Krishnamurthy5,10, Cristina Ivan3, Xiaoping Su4, Naoto T Ueno1,10, Steve VanLaere7, Francois Bertucci8, Debu Tripathy1,10, Pablo Vivas-Mejía9, Wendy A Woodward2,10, Bisrat G.Debeb1,10

1Department of Breast Medical Oncology UT MD Anderson Cancer Center, Houston TX, 2Department of Radiation Oncology UTMD Anderson Cancer Center, Houston TX, 3Department of Experimental Therapeutics UT MD Anderson Cancer Center, HoustonTX, 4Department of Bioinformatics and Computational Biology UT MD Anderson Cancer Center, Houston TX, 5Department ofPathology UT MD Anderson Cancer Center, Houston TX, 6Department of Biological Sciences, University of Texas at Brownsville,Brownsville TX, 7Department of Oncology, the University of Antwerp, Antwerpen, Belgium, 8Department of Medical andPredictive Oncology Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France, 9Department ofBiochemistry and Cancer Center, University of Puerto Rico (UPR), 10MD Anderson Morgan Welch Inflammatory Breast CancerClinic and Research Program

Background: Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer andaccounts for a significant 10 % of breast cancer deaths in the USA owing to its aggressive proliferationand metastasis, and a lack of effective therapeutic options. Unraveling the underlying mechanisms ofgrowth and metastasis of this aggressive disease could lead to effective therapeutic strategies for animproved outcome in IBC patients. We recently generated in vitro and in vivo IBC models for brainmetastasis studies [Debeb et al. JNCI, 2016] and observed a dramatic upregulation of Lipocalin 2(LCN2), a small, secreted iron-trafficking protein which plays a significant role in immune andinflammatory responses and the promotion of malignant progression. We hypothesized that LCN2facilitates tumor progression and metastasis in IBC. Methods: Stable knockdown (KD) of LCN2 in IBCcell lines was achieved with lentiviral vectors. Proteomic and gene expression profiling wereperformed using RPPA and Affymetrix Clariom D microarray. For in vivo studies, control and LCN2 KDIBC cells were transplanted into the cleared mammary fat pad of SCID/Beige mice. Tumor-skininvolvement was assessed visually during primary tumor growth and tumor excision. LCN2 geneexpression levels in clinical samples were analyzed from the IBC Consortium as well as public datasets. LCN2 serum levels in IBC patients were measured using ELISA and were correlated withclinicopathological variables and outcome data. Results: LCN2 gene expression is higher in IBC versusnon-IBC patients (p=0.00036), independently of the molecular subtypes, and higher in moreaggressive (TNBC and HER2+) than hormone receptor-positive subtypes (p<0.00001). LCN2 expressionin patient tissues is correlated with reduced overall survival (p<0.00001) and metastasis-free survival(p=0.04) in non-IBC; however, LCN2 was not associated with overall survival in IBC patient serumsamples. LCN2 expression was also significantly higher in IBC cell lines, in their culture media, and inbrain metastasis sublines compared to non-IBC cell lines (p=0.004). In IBC cell lines, LCN2 KD reducedproliferation, colony formation, migration, and cancer stem cell properties. In vivo silencing of LCN2in SUM149 cells inhibited primary tumor growth (p=0.001) and resulted in a well-differentiatedtumor histology. Additionally, SUM149 LCN2 KD significantly reduced skin invasion/recurrence (LCN2control vs LCN2 KD: 88 % vs 25 %, p=0.01) suggesting LCN2 is a mediator of tumorigenesis. Analysis ofproteomics data showed changes in major signaling pathways including PI3K-Akt signaling andEGF/EGFR signaling pathways. Mechanistically, LCN2 depletion in SUM149 abrogated EGF-inducedEGFR phosphorylation and ERK activation. Conclusions: Our findings suggest that LCN2 drives IBCtumor progression and skin invasion/recurrence potentially via the EGFR signaling pathway. Futurestudies will determine the role of LCN2 in metastasis and pinpoint the detailed mechanisms of LCN2-mediated IBC tumorigenesis and recurrence.

Email: esschlee@mdanderson.org

Emily Schlee Villodre, Ph.D. Breast Medical OncologyMD Anderson Cancer Center

Mentor: Dr. Bisrat Godefay Debeb

Research Interest:I study epigenetic alterations related to various diseases and development using computationalmethods.

Abstract:Tet protein mediated DNA methylation oxidation regulates ventricular chamber development

Shaohai Fang#1, Jia Li#1, Yang Xiao2, Minjung Lee1, Wei Han1, Tingting Li1, Matthew C. Hill3,Rang Xu1, Yubin Zhou2, Deqiang Sun1, James F. Martin3, Yun Huang1

1Center for Epigenetics & Disease Prevention, Institute of Biosciences and Technology, Collegeof Medicine, Texas A&M University, Houston, TX 77030, USA, 2Center for Translational CancerResearch, Institute of Biosciences and Technology, College of Medicine, Texas A&M University,Houston, TX 77030, USA, 3Cardiovascular Research Institute, Baylor College of Medicine,Houston, TX 77030, USA

Cardiac differentiation during development is tightly regulated through precise control overgene expression when cells receive a multitude of intracellular and extracellular cues. The Ten-Eleven Translocation (TET) protein-mediated DNA methylation oxidation plays an importantrole in regulating DNA methylation and demethylation homeostasis during development. HowTET regulate the expression of key genes during embryonic heart development is still unclear.Here, we generated a cardiac-specific Tet2/3-deficient mouse model (Tet2/3-DKO). Deletion ofTet2 and Tet3 in murine cardiomyocytes (CMs) is embryonically lethal. Detailed morphologyanalysis with embryonic heart tissue showed that Tet2/3-DKO embryos displayed aberrantventricular trabeculation and compaction. Bulk and single-cell transcriptome analysis showedsignificant decreased expression of cardiac development related genes and dramatic reductionof CMs in Tet2/3-DKO embryonic heart. Further epigenomic analysis exhibited strongdecreased 5hmC level and chromatin accessibility at distal-regulatory regions of cardiacdevelopmental related genes. The motif analysis in the affected genomic regions showedsignificantly enrichment of YY1 binding motifs. Further biochemical and high-throughputsequencing analysis confirmed decreased chromatin association of YY1 in Tet-deficient cells.Since YY1 has been reported in regulating higher-order chromatin structure, we furtherinvestigated genome architecture in Tet2/3-DKO embryonic CMs by HiChIP. We observedimpaired long-range contacts at cardiac developmental related genes in Tet2/3-DKO embryonicCMs. In summary, we unveiled previous unrecognized functions of Tet-mediated DNAhydroxymethylation in regulating chromatin accessibility to facilitate the genomic recruitmentof key transcription factor, YY1 (Ying-Yang 1), as well as long-range chromatin contacts atcardiac-specific genes during murine embryonic heart development.

Email: jli@ibt.tamhsc.edu

Jia Li, Ph.D. Center for Epigenetics & Disease PreventionTexas A&M Health Science Center

Mentor: Dr. Deqiang SunDr. Yun Huang

Research Interest:

My research interests are developing predictive and prognostic nutritional biomarkers for

pediatric cancer patients using both targeted and non-targeted metabolomics approaches, andidentifying perinatal and early life risk factors for pediatric cancers, with emphases oncongenital anomalies and infant and child nutrition.

Abstract:Metabolomic profiling improves prediction of minimal residual disease and reveals potentialmetabolic vulnerabilities in pediatric acute lymphoblastic leukemia

Jeremy Schraw1, Jacob Junco2, Austin Brown2, Michael Scheurer2, Karen Rabin2, Philip Lupo2

1Baylor College of Medicine, Department of Medicine, Section of Epidemiology and PopulationSciences, 2Baylor College of Medicine, Department of Pediatrics, Section of Hematology-Oncology

Background/Objectives: End-induction minimal residual disease (MRD) is the most importantpredictor of relapse in pediatric acute lymphoblastic leukemia (ALL). However, many relapsesoccur in MRD-negative patients. We hypothesized that global metabolomic profiling ofdiagnostic bone marrow plasma could improve prediction of MRD and provide insights into thebiology of relapse.Design/Methods: We retrospectively identified 99 patients diagnosed and treated at TexasChildren’s Hospital from 2007-2015, of whom 39 were MRD positive and 60 were MRD-negative at end induction, using a cut-off of 0.01%. Diagnostic bone marrow plasma wassubjected to metabolomic profiling via UPLC-MS/MS. We used the nonparametric Kruskal-Wallis test to compute univariate p-values comparing MRD-positive vs. negative plasma, andmetabolite set enrichment analysis (MSEA) to identify pathways enriched for differentiallyabundant metabolites with KEGG as the reference. Metabolites with univariate p-values ≤0.001were evaluated in logistic regression models for MRD, and the best predictors were obtainedby backward elimination. We assessed the performance of models for MRD using clinicalfeatures alone and clinical features + metabolites via DeLong’s test for correlated receiveroperating characteristics curves. We measured the in vitro cytotoxicity of drugs targeting top-scoring pathways in ALL cell lines using flow cytometric staining for Annexin-V/propidiumiodide.Results: MSEA revealed central carbon metabolism to be the pathway most enriched fordifferentially abundant metabolites (p=4.00E-06). The constituent metabolites pyruvate,succinate, fumarate, and malate were each significantly increased in MRD positive patients(p≤0.001). A predictive model for MRD incorporating these metabolites outperformed clinicalfeatures alone (AUC of 0.86 vs 0.73, p=0.001). FK866, an NAMPT inhibitor which depletes thesemetabolites, demonstrated significant cytotoxicity in 5 of 6 ALL cell lines (IC50s 1-10 nM).Conclusion: Metabolomic profiling improved prediction of subsequent MRD and identifiedpotentially druggable metabolic alterations. If validated, these biomarkers may improve riskprediction and our understanding of disease biology.

Email: Schraw@bcm.edu

Jeremy Schraw, Ph.D. Department of MedicineBaylor College of Medicine

Mentor: Dr. Michael Scheurer

Research Interest:The major focus of my research is identification of therapeutic vulnerabilities in cancer and studyingmechanisms of sensitivity/resistance to targeted therapies. My long term goal is to identify andunderstand the molecular changes that drive the malignancy in solid tumors, with the hopes ofexploiting these changes to design effective therapy that can be translated to clinic.

Abstract:Susceptibility of NOTCH1 mutant head and neck squamous carcinoma to PI3K/mTOR pathwayinhibition via PDK1Vaishnavi Sambandam1, Mitchell J. Frederick4, Li Shen2, Pan Ton2, Shaohua Peng1, TuhinaMazumdar1, Curtis R. Pickering3, Jeffery M3, Jing Wang2, Faye M. Johnson1

1Department of Thoracic/Head & Neck Medical Oncology, he University of Texas MD Anderson Cancer Center, Houston, USA.,2Department of Bioinformatics and Computational Biology, he University of Texas MD Anderson Cancer Center, Houston, USA.,3Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA., 4Department ofOtolaryngology, Baylor College of Medicine, Houston, Texas, USA

Genomic alterations in the PI3K/mTOR pathway occur in 54% of head and neck squamous cell carcinoma(HNSCC) patients. To identify novel biomarkers of response to PI3K/mTOR pathway inhibitors in HNSCC,we tested the efficacy of seven PI3K/mTOR pathway inhibitors in 59 HNSCC cell lines and determined theassociation between drug sensitivity and genomic alterations. We identified that NOTCH1MUT lines weresignificantly sensitive to the following PI3K/mTOR pathway inhibitors: GSK2126458 (12/14 lines), BYL719(6/14), PQR309 (12/14), BKM120 (14/16), BEZ235 (12/16), BAY806942 (13/14), and GDC0980 (5/14). Incontrast to PIK3CAMUT cell lines, NOTCH1MUT lines underwent significant apoptosis in addition to G1/S cellcycle arrest after PI3K/mTOR pathway inhibition. NOTCH1MUT lines also showed significantly reducedclonogenic growth in vitro and significant tumor growth inhibition in vivo in both oral orthotopic andsubcutaneous xenograft mouse models. We employed CRISPR-Cas9 gene editing technology to knock outNOTCH1 gene in two NOTCH1WT lines, PJ34 and UMSCC49. After GSK2126458 treatment, NOTCH1-KOlines showed decreased cell viability compared to parental lines. PJ34 NOTCH1 knock out line showedsignificantly increased apoptosis after PI3K/mTOR inhibitors compared to parental lines (GSK2126458:1.62-fld increase, P=0.003, BEZ235: 2.63-fld increase, P=0.003).UMSCC49 NOTCH1 knock out cells alsoshowed significantly increased apoptosis after PI3K/mTOR inhibition (GSK2126458: 1.37-fld increase,P=0.002, BEZ235: 1.44-fld increase, P-0.0001). Both NOTCH1 KO lines also showed increased cleavedPARP and cleaved caspase 3 by western blot analysis. With PJ34 NOTCH1 knock out lines, bothGSK2126458 and BEZ235 treatment significantly decreased number of colonies (GSK2126458:1.35-flddecrease, P<0.005-; BEZ235: 1.55-fld, P<0.005). UMSCC49 NOTCH1 knock out lines also showeddecreased colonies after PI3K/mTOR inhibition (GSK2126458: 16.2-fld, P<0.0001, BEZ235: 2.8-fld,P<0.00001). As no canonical pathways account for the underlying mechanism of sensitivity, we measuredthe level of 301 proteins by reverse phase protein array (RPPA) in three NOTCH1MUT and three NOTCH1WT

lines after GSK2126458 treatment. Several proteins were differentially regulated in NOTCH1MUT cellscompared with wild-type lines including PDK1, FoxM1 and phospho-ERK. We then investigated PDK1because it is activated by PI3K, and can regulate FOXM1, ERK, and p70 ribosomal protein S6 kinase(p70S6K) which were also inhibited more robustly in NOTCH1MUT HNSCC. To test the role of PDK1 inPI3K/mTOR inhibition, we over expressed PDK1 in NOTCH1MUT cells and the presence of PDK1-GFP wasconfirmed by western blot analysis. PDK1 overexpression in NOTCH1MUT cells successfully led todecreased apoptosis after GSK2126458 treatment as compared to the parental lines. The combination ofAKT and PDK1 inhibition led to decreased cell viability in all four NOTCH1WT lines tested as compared tosingle agents. The combination also led to significantly increased apoptosis in all NOTCH1WT cell linestested as demonstrated by cleaved PARP and cleaved Caspase 3 levels by western blot analysis. This workis significant because inactivating NOTCH1 mutations, which occur in 18% of HNSCC patients and insquamous cell carcinomas of the lung, esophagus, and other sites, may serve as a biomarker for response.Our present work may uncover important combination therapies for HNSCC.

Email: vsambandam@mdanderson.org

Vaishnavi Sambandam, Ph.D.Department of Thoracic Head and Neck Medical OncologyMD Anderson Cancer Center

Mentor: Dr. Faye M. Johnson

Research Interest:My current research interest is focused on identifying the biological mechanism(s) of theresistance to CDK4/6 inhibitors and to identify independent biomarkers to predict responseand/or resistance.

Abstract:Combined inhibition of STAT-3 and DNA repair in palbociclib resistant ER-positive breastcancer cellsNicole M. Kettner1, Smruthi Vijayaraghavan1, Merih Guray1, Tuyen Bui1, Min Jin Ha2, Bin Liu3,Min Yi4, Jason P.W. Carey1, Xian Chen1, Kris Eckols5, Akshara S. Raghavendra6, Nuhad K.Ibrahim6, Meghan Karuturi6, Stephanie S. Watowich7, Aysegul A. Sahin8, David J. Tweardy5,9,Kelly K. Hunt4, Debu Tripathy6, Khandan Keyomarsi11Department of Experimental Radiation Oncology, 2Department of Biostatistics, 3Department of Human Genetics, 4Departmentof Breast Surgical Oncology, 5Department of Infectious Diseases, 6Department of Breast Medical Oncology, 7Department ofImmunology, 8Department of Pathology, 9Department of Internal Medicine

The CDK4/6 inhibitor palbociclib is currently being used in combination with endocrinetherapy to treat advanced ER positive breast cancer patients. While this treatment has showngreat promise in the clinic, about 25-35% of the patients do not respond initially, and almost allpatients eventually acquire resistance. Hence, understanding the mechanism(s) of acquiredresistance to CDK4/6 inhibition is crucial to devise alternate treatment strategies. Tointerrogate this, we developed MCF7 and T47D palbociclib resistant cells. These cells not onlyare resistant to palbociclib, but cross resistant to the other CDK4/6 inhibitors; ribociclib andabemaciclib, suggesting common mechanisms of resistance for this class of inhibitors.Genomic, transcriptomic, and proteomic analysis revealed enrichment of pathways known toregulate EMT and cancer stem cells (CSCs), as well as, downregulation of estrogen responseand DNA repair pathways. Palbociclib resistant cells exhibited mammosphere formation andCD44high/CD24low population indicating the presence of increased CSCs. Given the recentlyelucidated role of IL-6/STAT-3 mediated CSCs in drug resistance, we examined IL-6 mRNAlevels, which increased by >12-fold in the resistant cells. Treatment with STAT-3 inhibitors,Napabucasin and C188-9, significantly decreased the CSC population and mammosphereformation, indicating a crucial role for the IL-6/STAT-3 pathway in driving CSCs and palbociclibresistance. Since DNA repair pathways were collectively downregulated in the palbociclibresistant cells, we examined their sensitivity to DNA damaging agents. Results showed thatresistant cells were more sensitive to olaparib (PARP inhibition), with no effect on CSCs. Next,we examined if combined treatment with agents targeting IL-6/STAT-3 and DNA repairpathways would be synergistic in palbociclib resistant cells. Results show that combinedtreatment with olaparib and napabucasin significantly decreased CSC population, colonyformation and increased cell death via apoptosis, when compared to no-treatment or singletreatment controls of the palbociclib resistant cells. Lastly, we interrogated tumor samplesfrom breast cancer patients who progressed while on palbociclib (25 matched pre- and post-progression samples) for the deregulation of ER, DNA repair and IL-6/STAT-3 pathways andfound that these pathways are also altered in patients with acquired or intrinsic resistance topalbociclib. Taken together, the results show that targeting IL-6/STAT-3 mediated cancer stemcells and DNA repair deficiency by PARP inhibitors in combination can effectively treat acquiredresistance to palbociclib.

Email: nmkettner@mdanderson.org

Nicole Kettner, Ph.D. Experimental Radiation OncologyMD Anderson Cancer Center

Mentor: Dr. Khandan Keyomarsi

Research Interest:To study the influence of the gut microbiota as it relates to therapeutic efficacy of immunecheckpoint blockade.

Abstract:Implications for clinical trial design based on host factors and variation of the gut microbiomeof complete responders to immune checkpoint blockade and healthy individuals

V.Gopalakrishnan1, B.A. Helmink1, P.O. Gaudreau1, C.S. Spencer2, A.L. Harris1, J.L. McQuade1, M.C. Andrews1,A.P. Cogdill1, V.B. Jensen1, A.F. Duran1, T. Heffernan1, M.A. Jamal1, I.C. Claudia1, H. Tawbi1, R.N. Amaria1,M.K.K. Wong1, R. Arora1, E.M. Burton1, E. Sirmans1, R.R. Jenq1, J.E. Gershenwald1, M.A. Davies1, J.A. Wargo1

UT MD Anderson Cancer Center Parker Institute for Cancer Immunotherapy

Background: The gut microbiome has been shown to have profound influences on host and anti-tumorimmunity, and pre-clinical studies suggest that gut microbiota may be modulated to enhance responsesto immune checkpoint blockade. Recent studies demonstrate differences in the baseline gutmicrobiome of responders (R) versus non-responders (NR) to anti-PD-1 therapy in patients, withidentification of a unique compositional signature associated with a 100% response rate (Type-1).Several clinical trials are in development / underway that aim to modulate the microbiome to augmentresponses to immune checkpoint blockade. These are, in part, based on foundational evidence thattreatment with fecal microbiota transplant (FMT) from healthy donors is associated with clinicalresponses in other diseases (C. difficile infection and inflammatory bowel disease, CDI and IBD);however, the optimal donors for FMT to enhance responses to immune checkpoint blockade remainincompletely understood, as is the influence of dietary and lifestyle factors on this population.Methods: We assembled a large cohort of early and late-stage melanoma patients (n=312) initiatingsystemic treatment at UT MD Anderson Cancer Center. In addition to biological specimens, we collecteda comprehensive lifestyle survey, including the NCI dietary screener questionnaire, in a subset (n=113).The fecal microbiome was characterized via sequencing of the V4 region of the 16S rRNA gene todetermine diversity and compositional structure, and comparisons were made between melanomapatients and healthy controls. Lastly, fecal microbiota transplant (FMT) of selected complete responders(CR) donors versus a known NR (n=3 and 1, respectively) was performed into gnotobiotic mice andmelanoma tumors were implanted. Mice were then treated with immune checkpoint blockade. Tumoroutgrowth was assessed and longitudinal microbiome analyses in FMT-treated mice were alsoperformed. Results: Characterization of gut microbiota revealed wide variation in composition (p<0.01)of the gut microbiota, with a trend towards higher diversity (p=0.2) in CR donors versus healthy controls.Furthermore, in melanoma patients “biotic” use, defined as self-reported use of either biotic was quitecommon (29% antibiotics, 42% probiotics), and was associated with lower alpha-diversity (p=0.01), withsignificant associations observed for both antibiotics alone (p=0.05) and for probiotics alone (p=0.02).Interestingly, not all CRs demonstrated a Type-1-like signature (with higher relative abundance ofClostridiales versus Bacteroidales) (27%, n=3/11) nor did healthy controls 28% (n=33/116). This hascritical implications for FMT donor selection in immune checkpoint blockade trials (versus those for CDIor IBD). Murine studies demonstrated reduced tumor growth in CR-FMT mice vs. NR-FMT mice, withvariability noted between donors. Immune profiling in available patient tumor samples and in murinestudies and comparisons to gut microbiota are currently being performed. Conclusions: These dataprovide preliminary evidence that the gut microbiome of melanoma patients may be modifiable by hostfactors, and provide important information about potential donor selection in FMT trials inimmunotherapy, warranting additional studies and translational research.

Email: vgopalakrishnan1@mdanderson.org

VancheswaranGopalakrishnan, Ph.D. Department of Surgical OncologyMD Anderson Cancer Center

Mentor: Dr. Jennifer A. Wargo

Breakout Sessions

Main Building R11.1100 Ballrooms 5 & 6

Making the Most of Your Postdoc

WORKSHOP: Negotiation skills for your career and a better work-life balancewith Lydia Musher, MS,MBA

Knowing how to negotiate is an important skill to have as it can help with professional development and career advancement, resolving conflicts, problem solving, communication and persuasion. As postdocs this skills are important when it comes to our mentors, colleagues, collaborators, etc.

Main Building R11.1100 Ballrooms 7 & 8

Grants: Navigating the Process Pre- and Post-Awardwith Rama Soundararajan, PhD, Steven Millward, PhD, Sanjay

Shete, PhD, Sarah Fayle, MA,MS, and Prerna Malaney, PhD

Get insights and advice on writing grants/fellowships, the process in applying as well as learn about what happens when you get the award.

Posters

Poster PresentationsNumber Name Title

(Morning session – 11:00-11:40a)

1 Stefano Casarin A Hybrid Agent-Based, Particle and Partial Differential Equations Method to Analyze Vascular Adaptation

3 Onyema Greg Chido-Amajuoyi

Prevalence and Correlates of Colorectal Cancer Screening using FOBT/FIT at Home versus in Physician’s Office

5 Andre Schultz SAMMI: An Interactive, Semi-Automated Tool for the Illustration and Visualization of Biological Networks.

7 Hai Shu Extracting common and distinctive structures from high-dimensional correlated datasets

9 Seemana Bhattacharya Inhibition of Autophagy Kinase ULK1 Combined with Chemotherapy Results in Modulation of Reactive Oxygen Species and DNA Damage Response to Induce Synergistic Cell Death in Acute Myeloid Leukemia

11 Dalnim Cho Concordance and discordance of lifestyle factors among African American heterosexual couples

13 Carminia Della Corte Cisplatin treatment induces anti-tumor immune response in NSCLC by activation of the innate immune response pathway

15 Dai Ogata The expression of MIF-regulated inflammatory markers in Stage Ⅳmelanoma: Risk of CNS metastasis and survival

17 Meagan Whisenant Patients’ Preference of Cancer Symptom Patient Reported Outcomes Measures

19 Ivan Castello Serrano A RUSH to the raft: secretory trafficking mediated by membrane microdomains.

21 Mei-Ju Chen Identification of pseudogenes involved in response to PD-1/PD-L1 blockade

23 Alfredo Erazo-Oliveras Emerging role for membrane therapy in shaping aberrant Wnt signaling

25 Monica Goss UBE4B regulates Amyloid Beta generation and secretion in Alzheimer's Disease

Poster PresentationsNumber Name Title

(Morning session continued)

27 Priyamvada Jayaprakash Targeted hypoxia reduction restores T cell infiltration and sensitivity to immunotherapy in prostate cancer

29 Fernanda Kugeratski Quantitative analysis of the proteomic content of exosomes from distinct cell sources

31 Xubin Li Perturbations of cell signaling networks reveal long-range and combinatorial interactions

33 Jessica Luzwick RAD51C mediated mitochondrial DNA fork protection surpasses inflammation

35 Enrica Marmonti Sphingosine-1-Phosphate Receptor 1 in exercise-induced tumor vascular remodeling.

37 Lisa Mustachio Defining the Role of GCN5 in Lung Cancer

39 Jihyun Park Non-phosphorylatable PEA15 reverts epithelial-mesenchymal transition (EMT) induced in triple negative breast cancer by regulating IL-8 expression

41 David Peng PD-L1 checkpoint blockade in combination with MEK inhibition reduces lung cancer metastasis

43 Justin Roberts The Role of Activated Beta-catenin/Wnt Signaling in the Progression of Castration Resistance of Prostate Cancer in Bone

45 Douglas Senna Engelke Neural Circuits Regulating Food-Seeking Behavior in a Threatening Environment

47 Clara Sinel Inhibition of Enterococcus faecalis pathogenicity and biofilm formation by Candida albicans

49 Yumeng Wang Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer

51 Zhan Xu Optimization of Radial Echo Planar Spectroscopic Image (rEPSI) Reconstruction for Hyperpolarized [1-13C]-Pyruvate Imaging

53 Dhurjhoti Saha SWI/SNF chromatin remodeler regulates RNA polymerase pausing in mouse embryonic stem cells

Poster PresentationsNumber Name Title

(Afternoon Session – 3:20-4:00p)

2 Corrine Ying Xuan Chua Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy for cancer treatment

4 Kerri-Anne Parkes Patient-centeredness in Cancer Care: Exploratory Factor Analysis of Patient-Centered Cancer Care Measures to Support Improved Care Quality

6 Anushree Sharma Tobacco use and its impact on breast cancer screening behavior

8 Sheeba Sujit Automated image quality evaluation of structural brain magnetic resonance images using deep convolution neural networks

10 Alicia Blessing Crizotinib eliminates dormant, autophagic ovarian cancer cells

12 Qiao Chu The inter-relationships among PTSD symptom clusters in an expressive writing intervention for Chinese American breast cancer survivors

14 Yuki Nishida TP73 isoforms (TAp73 and ΔNp73) are overexpressed in acute myeloid leukemias and potential therapeutic targets to enhance anti-leukemia activities of Bcl-2 and MDM2 inhibitors

16 Kavya Ramkumar Targeting AXL sensitizes NSCLC to ATR inhibitors by enhancing replication stress

18 Gaelle Auguste BET bromodomain protein 4 as a novel therapeutic target in dilated cardiomyopathy in laminopathy

20 Deepavali Chakravarti Telomere dysfunction is a driver of inflammatory bowel disease

22 Caroline Cvetkovic Investigating the Efficacy of Electrical Stimulation on Human Neural Networks to Promote Neuroregeneration

24 Natividad Fuentes Long chain n-3 fatty acids attenuate oncogenic KRas-driven proliferation by altering plasma membrane nanoscale proteolipid composition

26 Khushboo Irshad FAT1-REST exhibit a context-dependent relationship in glioblastoma

Poster PresentationsNumber Name Title

(Afternoon Session continued)

28 Aparna Krishnavajhala The loss of vector competency and transmission of the relapsing fever spirochete, Borrelia turicatae, in association with in vitro cultivation: implications for mutagenesis studies.

30 Chunlai Li LINK-A interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors

32 Tonghui Lin Hop2 is a Novel Physiological Partner of Osteoblast Terminal Differentiation Factor ATF4

34 Jiacheng Ma HDAC6 Inhibition Prevents Cisplatin-Induced Peripheral Neuropathy in a T Cell-Dependent Manner

36 Lisa Matz The exoribonuclease PNPase stabilizes small regulatory RNAs in Escherichia coli

38 Kapere Ochieng MBIP promotes cell motility and metastasis in Kras/p53 mutant non-small cell lung cancer

40 Somnath Paul Structural analysis of the INO80 chromatin-remodeling complex and distinctive role of the actin related proteins (ARPs)

42 Shivanand Pudakalakatti Early detection of pancreatic cancer by targeted molecular MRI Imaging of hyperpolarized silicon nanoparticles

44 Ozgur Karakuzu Novel Regulators of Oxidative Stress Response During Bacterial Infection

46 Vrutant Shah Targeting TRIM24-driven Mammary Carcinosarcomawith small ligand-coupled protein degraders

48 Karl-Heinz Tomaszowski Novel FancO/Rad51c anemia mouse model reveals gender-specific mortality.

50 Hongyin Wang Phosphatidylserine (PS) Externalization Facilitates Membrane Vesiculation Through Decreasing Membrane Stiffness

52

54

Monika Zelazowska

Sunetra Roy

Gammaherpesvirus infected B cells display abnormal repertoire

Molecular mechanism of RAD51C (FANCO) mediated replication fork protection

All postdoctoral fellows in The University of Texas MD AndersonCancer Center are automatically members of the PostdoctoralAssociation (PDA) and the National Postdoctoral Association (NPA).The PDA Executive Committee (PDAEC) strives to improve, enhance,and enrich the postdoctoral fellowship experience at MD Anderson byplanning monthly events, annual science and career symposia, andfostering interactions between members of the Texas Medical Center(TMC) through social and career development events.

Ways to contact the PDA and find information:

• http://www.mdanderson.org/postdocs

• postdoctoralassociation@mdanderson.org

• http://www.facebook.com/#!/groups/83955564561/

MD Anderson Cancer CenterPostdoctoral Association

Acknowledgements

The MD Anderson PDAEC would like to extend congratulations andformal gratitude to Dr. Peter Pisters, MD Anderson President, for hissupport and encouragement of all MD Anderson trainees.

Furthermore, we would like to thank Dr. Diane Bodurka, VP ofEducation, and the MD Anderson Department of Faculty andAcademic Development, and the Alumni and Faculty Association(AFA) for their generous sponsorship and assistance with this event.We appreciate the effort it took to secure the funding necessary tohelp establish and execute this symposium. The PDAEC would alsolike to thank MD Anderson Postdoctoral Advisory Committee forproviding endless assistance and mentorship throughout the year.

We would also like to recognize the contributions of Education andTraining, especially Dr. Victoria McDonnell, Office of PostdoctoralAffairs and Development, and Vondalyn Hall. Additionally, we thankMartha Skender in Education and Training for supporting theinception of APSS eight years ago and the teams in CreativeCommunications, especially Barry Smith of Photography Services andJeff Flasik for creating professional symposium materials.

We are indebted to the faculty judges for their constructiveevaluation and feedback for our participants. We also thank thepostdoctoral fellow judges for their feedback and review of posterand oral presentations.

We thank Drs. Omkara Veeranki, Elizabeth Menton-Deweese, RajanChaudhari, Yaohua Zhang, Emmanuela Gentile, Matthias Degroote,Jaya Aseervatham, Nicholas Murphy, Luis Alberto Vega, Seong HeePaek, Irene Guijarro, Zhenghu Chen, Ling Tao, Alison Massie, AlbertHunt, Sirisha Marreddy, Jaya Punetha, Angela Rynne Vidal, Yu Xiang,Alessandra Audia, Tara Dobson, and Zaker Schwabkey for theirefforts in our abstract organization and reviewing process.

In addition we would like to thank Fourwaves and its co-founder Dr.Matthieu Chartier for sponsoring us. Through Fourwaves we wereable to conduct registration, abstract submission, nametags, andbooklet assembly. We appreciate their support.

Finally, a big thank you to all of the members of PDAEC and speciallyour outgoing chairs Dr. Rajan Chaudhari and Dr. Kylee Veazey - thissymposium was made possible by all your hard work, organization,and support.

2018 APSS Organizing Committee

Dr. Daisy Izaguirre, Chair

Dr. Alessandra Audia, Vice-Chair

Dr. Rajan Chaudhari, Member

Dr. Kylee Veazey, Member

Dr. Lisa Mustachio, Member

Dr. Vrutant Shah, Member

Dr. Shivanand Pudakalakatti, Member

Dr. Robiya Joseph, Member

Dr. Omkara Veeranki, Member

Dr. Anca Chelariu-Raicu, Member

Acknowledgements

The Mission of APSS

The Annual Postdoctoral Science Symposium (APSS) was initiated on August 4th 2011, by the MD Anderson Postdoctoral Association to provide a platform for talented postdoctoral fellows to present their work to a wider audience.

APSS is a scientific symposium that incorporates all Texas Medical Center affiliated institutions. Our goal is to provide postdoctoral scientists across the entire Texas Medical Center a unique opportunity to learn, interact and develop new collaborations.