BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
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NAME: Chandran, Uma
eRA COMMONS USER NAME (credential, e.g., agency login): chandran201
POSITION TITLE: Visiting Research Associate Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION / DEGREE
(if applicable) / Completion Date
MM/YYYY / FIELD OF STUDY
University of California, Berkeley, CA / MPH / 06/1982 / Public Health
University of Pittsburgh, Pittsburgh, PA / PhD / 12/1990 / Biology
University of Pittsburgh, Pittsburgh, PA / MSIS / 06/1999 / Information Science
A. Personal Statement
I have extensive experience in both bench research and bioinformatics and co-direct the Cancer Bioinformatics Service (CBS), a translational core service at the University of Pittsburgh Cancer Institute. This highly utilized service, with over 30 users in 2014 alone, provides data analysis support for all genomic platforms, High Performance Computing (HPC) infrastructure for genomics data and develops data warehouses for integrating genomic and clinical data. I have deep experience working with all aspects of genomics data, and have analyzed data from all Next Generation Sequencing (NGS) platforms including RNA Seq, Whole Exome Seq (WXS) and Whole Genome Seq (WGS). I have performed integrative analysis across multiple platforms and from large consortia datasets such as TCGA, and am a key member of the Pittsburgh Genome Resource Repository (PGRR), a regulatory, hardware and software infrastructure for TCGA data. I have collaborated on multiple genomics projects with University of Pittsburgh investigators and I look forward to collaborating on the expression studies in your proposal to study MKL’s role in angiogenesis.
1. / Gau DM, Lesnock JL, Hood BL, Bhargava R, Sun M, Darcy K, Luthra S, Chandran U, Conrads TP, Edwards RP, Kelley JL, Krivak TC, Roy P. BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility - A proteomics study. Cell Cycle (Georgetown, Tex.). 2015 Apr 30; 0. doi: 10.1080/15384101.2015.1036203 PMID: 25927284 PMCID: PMC46149522. / Manohar R, Li Y, Fohrer H, Guzik L, Stolz DB, Chandran UR, LaFramboise WA, Lagasse E. Identification of a candidate stem cell in human gallbladder. Stem Cell Research. 2015 May; 14 (3):258-269. doi: 10.1016/j.scr.2014.12.003 PMID: 25765520 PMCID: PMC4439375
3. / Krill-Burger JM, Lyons MA, Kelly LA, Sciulli CM, Petrosko P, Chandran UR, Kubal MD, Bastacky SI, Parwani AV, Dhir R, LaFramboise WA. Renal cell neoplasms contain shared tumor type-specific copy number variations. The American journal of pathology. 2012 Jun; 180 (6):2427-39. PMCID: PMC3378847
B. Positions and Honors
Positions and Employment
03/1991 - 08/1998 / Senior Research Associate, Biological Sciences, University of Pittsburgh, Pittsburgh, PA11/1998 - 12/1999 / Application Developer, Computerm Corporation, Pittsburgh, PA
05/2000 - 12/2000 / Scientific Curator, Proteome Inc., Beverly, MA
05/2000 - 12/2000 / Scientific Consultant, MSA Corporation, Pittsburgh, PA
03/2001 - 06/2006 / Systems Programmer, Department of Pathology, University of Pittsburgh, Pittsburgh, PA
06/2006 – 06/2007 / Systems Programmer, Department of Biomedical Informatics, University of Pittsburgh, PA
07/2007 – 12/2015 / Research Associate, Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA
12/2015 – Present / Visiting Research Associate Professor, Department of Biomedical Informatics, University of Pittsburgh, PA
09/1/2004 - Present / Co-Director, Cancer Bioinformatics Services, Biomedical Informatics, University of Pittsburgh Cancer Institute, Pittsburgh, PA
Other Experience and Professional Memberships
05/15/2015 - Present / Member, American Medical Informatics Association05/15/2015 - Present / Member, Association of Biomolecular Resource Facilities
Honors
1991 - 1992 / Post-Doctoral Fellowship in Reproductive Physiology, Institutional National Research Service Award (NRSA) IT32HD)7332 - Center for Reproductive Physiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA1992 - 1994 / National Research Service Award (NRSA) IF32HDO7593-01A1
1996 - 1996 / Endocrine Society Travel Award to present at the 10th International Congress of Endocrinology, San Francisco, CA
C. Contribution to Science
1. / From 2001 to 2005, I was a member of the group, in the Department of Pathology, which participated in NCI’s Director Challenge project on prostate cancer. This was one of the first projects to analyze cancer microarray data with large sample sizes. We were one of the first groups to demonstrate that tissue adjacent to prostate tumors, although appearing normal, express gene expression profiles resembling prostate cancers and also demonstrated distinct molecular changes in metastatic versus organ confined cancers. In collaboration with Arul Chinnaiyan’s group at the University of Michigan performed one of the first integrative studies examining protein and gene expression in prostate cancers.a. / Day RS, McDade KK, Chandran UR, Lisovich A, Conrads TP, Hood BL, Kolli VS, Kirchner D, Litzi T, Maxwell GL. Identifier mapping performance for integrating transcriptomics and proteomics experimental results. BMC bioinformatics. 2011; 12:213. PMCID: PMC3124437
b. / Chandran UR, Ma C, Dhir R, Bisceglia M, Lyons-Weiler J, Liang W, Michalopoulos GK, Becich MJ, Monzon FA. Gene expression profiles of metastatic prostate cancer reveals disregulation of specific molecular pathways. BMC Cancer. 2007; 7:64.
c. / Varambally S, Yu J, Laxman B, Rhodes DR, Mehra R, Tomlins SA, Shah RB, Chandran U, Monzon FA, Becich MJ, Wei JT, Pienta KJ, Ghosh D, Rubin MA, Chinnaiyan AM. Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer cell. 2005 Nov; 8 (5):393-406.
d. / Chandran UR, Dhir R, Michalopoulos GK, Becich MJ, Gilbertson JR, Ma C. Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors. BMC Cancer. 2005; 45.
2. / As a result of these very extensive microarray analysis studies, I developed the CBS core service for UPCI and expanded our high throughput analysis to other tumors. We also expanded our expertise to additional microarray copy number and SNP analysis. CBS is one of the most highly utilized service within UPCI with over dozen users per year and my publications span a number of cancer disease groups at UPCI.
a. / Li J, Luthra S, Wang XH, Chandran UR, Sobol RW. Transcriptional profiling reveals elevated Sox2 in DNA polymerase ß null mouse embryonic fibroblasts. American journal of cancer research. 2012; 2 (6):699-713. PMCID: PMC3512183
b. / Lisovich A, Chandran UR, Lyons-Weiler MA, LaFramboise WA, Brown AR, Jakacki RI, Pollack IF, Sobol RW. A novel SNP analysis method to detect copy number alterations with an unbiased reference signal directly from tumor samples. BMC medical genomics. 2011; 4:14. PMCID: PMC3041647
3. / CBS’s efforts have expanded to include integrative proteomic and genomic platforms, development of NGS pipelines, TCGA data analysis including integrative analysis of all TCGA platforms and development of an institutional wide high performance computation infrastructure to store and analyze high dimensional big data.
a. / Sikora MJ, Cooper KL, Bahreini A, Luthra S, Wang G, Chandran UR, Davidson NE, Dabbs DJ, Welm AL, Oesterreich S. Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response. Cancer Research. 2014 Mar 1; 74 (5):1463-74. PMCID: PMC3955299
b. / Mao P, Joshi K, Li J, Kim SH, Li P, Santana-Santos L, Luthra S, Chandran UR, Benos PV, Smith L, Wang M, Hu B, Cheng SY, Sobol RW, Nakano I. Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3. Proceedings of the National Academy of Sciences of the United States of America. 2013 May 21; 110 (21):8644-9. PMCID: PMC3666732
c. / Maxwell GL, Hood BL, Day RS, Chandran U, Kirchner D, Kolli VS, Bateman NW, Allard J, Miller C, Sun M, Becich MJ, Berchuck A, Kohn E, Risinger JI, Conrads TP. Proteomic analysis of stage I endometrial cancer tissue: Identification of proteins associated with oxidative processes and inflammation. Gynecol Oncol. 2011 Jun 1; 121 (3):586-94.
Complete List of Published Work in MyBibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/1BYWuoS2QOAAh/bibliography/44489353/public/?sort=date&direction=ascending
D. Research Support
Ongoing Research Support
9R01 CA186780 (Wang) / 04/01/14 - 03/31/19NIH
Roles of EAF2 in Androgen Action in the Prostate
Androgens play important roles in prostate development and two major diseases - prostate cancer and benign prostatic hyperplasia (BPH). Understanding the mechanism of androgen action may lead to new approaches of treatment and/or prevention of prostate cancer and/or BPH. This project is proposed to elucidate the cellular mechanisms of androgen action in the prostate, particularly the role of androgen-responsive gene EAF2. Our data, together with the observations of others, led to the research hypothesis that EAF2 and p53 act synergistically in modulating tumor suppression and AR signaling in the prostate. The success of this project may lead to new approaches to distinguish aggressive prostate tumors from indolent ones based on their status of EAF2, p53, and other important tumor suppressors and/or oncogenes. This project may also identify new therapeutic targets that are abnormally activated by current loss of EAF2 and p53 in prostate cancer.
P50 CA121973 (Kirkwood) / 08/26/08 - 06/30/18
NIH
Spore in Skin Cancer
The overall goals of the University of Pittsburgh Skin Cancer SPORE are to improve the prevention and treatment of skin cancers, focusing upon melanoma and cutaneous T cell lymphoma. The SPORE program will consist of five translational research projects in skin cancer, four cores including an administrative core, a developmental research program and a career development program. The University of Pittsburgh Skin Cancer SPORE will use an interdisciplinary approach to meet its objectives by carrying out projects with co-investigators in basic, applied and clinical science. It is also organ-specific in that its approach and all projects will test hypotheses about skin cancer molecular biology and progression, tumor immunobiology and treatment. The long-term translational research projects will serve as the basis for improving the outcome of patients with lethal skin cancers.
5R01 DK099320 (Fox/Locker) / 07/15/13 - 06/30/17
NIH
Regulation of HNF4 in Hepatic Failure in Cirrhosis
The cause of liver failure in cirrhosis is not well understood, as the liver is capable of regeneration and functions normally despite loss of more than half of its hepatocytes. We therefore hypothesize that restoration of HNF4 will effectively treat cirrhotic patients with end-stage liver failure by correcting the metabolic defects and reversing the hepatocyte replicative senescence. In these studies, we will use a recombinant AAV vector that encodes HNF4 driven from an inducible promoter to determine whether short term treatment with HNF4 can lead to sustained normalization of hepatic function and survival. In addition, we will assess the utility of HNF4-AAV treatment during continuing injury with CCL4 to determine the potential clinical efficacy of such therapy. To determine the mechanism of HNF4 down regulation in decompensated cirrhosis, we will perform a genome-wide ChIP-Seq analysis of isolated hepatocytes and whole liver. Finally, we will determine the extent to which human end-stage cirrhotic livers share the same characteristics as those identified in our rodent studies, and will determine the extent that restoration of HNF4 expression can normalize human hepatocytes derived from these end-stage livers.
R01 NS037704 (Pollack) / 04/01/10 - 01/31/17
NIH
Molecular Markers as Predictors of Outcome in Gliomas
The goal of this project is to analyze the association of molecular features with outcome in childhood malignant gliomas.
P30 CA047904 (Davidson) / 09/10/97 - 07/31/20
NIH/NCI
Cancer Center Support (CCSG)
The University of Pittsburgh Cancer Institute (UPCI) is a multidisciplinary cancer research center with programs in basic research, translational research and clinical investigations. Dr. Chandran directs the Cancer Informatics Services (CIS). The CIS has been continuously funded as part of the Cancer Center Support Grant (CCSG) funding at UPCI for 6 years and the CCSG grant has been in place for 22 years.
5R01 HD072189 (Plant) 02/01/16-01/31/17
NIH
Molecular Bases Committing Primate Spermatogonia to a Pathway of Differentiation
The long-term goal of this project is to understand the cellular and molecular mechanisms that control
spermatogonial differentiation in the rhesus monkey, a representative higher primate.
SAP4100070287 (Cooper) / 06/01/15 – 05/31/18
PA DOH
Big Data for Better Health (BD4BH) in Pennsylvania
Rapidly increasing volumes of molecular and electronic health record data in health care hold great promise for predicting patient outcomes, personalizing care, reducing geo-demographic disparities, and improving health. To realize this potential, the project will develop methods for merging, managing, utilizing, processing, analyzing, and sharing large amounts of diverse types of data by developing automated methods for extracting and representing patient-level data, including clinical text, about the course of disease. We will also develop and apply machine learning methods to large complex datasets to predict cancer outcomes based on constructed features that are biologically meaningful. In addition, plans are to partner with another PA institution in order to train underrepresented minority students in the analysis of Big Data.
Completed Research Support
U24 DK097748 (DeFranco) / 09/01/13 - 05/31/15NIH/NURSA
The Chromatin Landscape of Fetal Hypothalamic Neural Stem Cells
For the past few years we have examined glucocorticoid receptor (GR) function in cultured neural stem/progenitor cells (NSPCs) isolated from mouse embryos (E14.5) (i.e. neurospheres [NS]) as a model to examine molecular mechanisms of GC effects on cerebral cortical development. NS cultures are particularly advantageous for analysis of NSPC function since with subsequent passaging in vitro, they “mature” and adopt distinct progenitor cell fates that mimic those that occur in fetal and neonatal development. We propose to apply the knowledge and expertise that we have gained in this system to examine NS cultures from fetal hypothalamus. We hypothesize that long-term changes in hypothalamic regulation of reproduction and metabolism can result from GC-induced alterations in hypothalamic NSPC function. Three genome-wide approaches will be used to identify global alterations in the chromatin landscape of this unique NSPC population whose developmental programming me be altered by GC exposure.
U01 HL112707 (Kaminski) / 05/01/12 - 04/30/15
NIH
Sarcoidosis and A1AT Genomics & Informatics Center
To improve disease classification, facilitate biomarker discovery in Alpha-1 antitrypsin deficiency (A1AT), an autosomal recessive genetic disease that is associated with a variable risk of COPD, and Sarcoidosis, and accelerate advent of novel therapy an integrative approach that combines the results of clinical studies with molecular phenotyping results is required. The objectives will be addressed through two research projects. Project 1: A1AT microbiome - addresses the hypothesis that shifts in the lung microbiome determine the extent of lung involvement in A1AT and that they are reflected in mRNA and microRNA changes in surrogate tissues, and Project 2: Novel molecular phenotypes in Sarcoidosis - address the hypothesis that systemic inflammation as reflected in gene expression changes in PBMC is indicative of disease extent, microbiome shifts and granuloma molecular networks.