I was trained as a computational biologist with expertise in biology and computer science. At the University of California, Davis I was first exposed to 454-sequencing, to identify genetic variants, and the revolution of Next-generation Sequencing (NGS) technologies and large-scale data analysis. I quickly became aware of the amount of data that would be generated and the need for a robust and reproducible analysis pipelines. As I developed software and algorithms I also began to see the power of data integration for the purpose of elucidating biological mechanisms as well as the need of public data resources. Before re-entering bioinformatics, I spent two years as a software developer with Infosys. I developed and maintained a suite of large-scale customer relational management tools. This experience gave me insight into industry standards of software design and implantation as well as into data management. It also inspired me to apply these same standards to biological databases in research settings. Large quantitative datasets using global studies extend our knowledge of genes, their products and their interactions. By integrating quantitative datasets with curated, focused experimental and clinical data creates unique comprehensive databases. I have been involved in the design and implementation of databases, ENCODE (Encyclopedia of DNA Elements) and UCSC Genome Browser Projects, integrating scientific information into encyclopedic databases essential for investigation. While on these projects, I also implemented genomic analysis pipelines to facilitate reproducible data analysis in the Amazon Cloud (AWS). Using these approaches, I have been focused on the implementing, optimizing and distributing genomic analysis pipelines to facilitate reproducible data analysis.
In 2014, I moved to UT Southwestern Medical Center (UTSW) and took the opportunity of my position first as a computational biologist in the Green Center for Reproductive Biological Sciences and then in the Bioinformatics Core Facility to further understanding of the human genome by integration of large-scale functional and comparative genomics datasets in cancer. Specifically, in the Lonestar Oncology Network for Epigenetics Therapy and Research (LONESTAR) Consortium, I developed a multi-omics integration pipeline that identifies breast cancer subtype-specific transcription factors (TFs) bound at active enhancers that regulate gene expression patterns determining growth and clinical outcomes. I applied these approaches, in collaboration with Dr. Ping Mu (prostate cancer cell biology), to identify the enhancer landscape and key TFs driving prostate cancer resistance leading to new clinical targets. Currently, I am working on integrating multiple -omics assays to understand transcription factors driving gene regulatory networks in human cancers.
As the co-lead of the Data Analytics Core of the UT Southwestern Kidney Cancer SPORE (Dr. James Brugarolas), I developed the Kidney Cancer Explorer (KCE), facilitate hypothesis generation from clinical and genomic data. Using this framework for KCE, we aim at expanding this project to create a pan-cancer data commons (PC-DC), which will allow researchers to build patient cohorts based on clinical, pathological and genomic information, allowing researchers to identify molecular treads with clinical attributes or vice-versa.
- (2008), Biology
- Graduate School
- Johns Hopkins University (2011), Biology
- Chromatin structure and gene regulation
- Comprehensive Scientific Databases
- Data integration
- Reproducibility and Open Science
- Twist2 amplification in rhabdomyosarcoma represses myogenesis and promotes oncogenesis by redirecting MyoD DNA binding.
- Li S, Chen K, Zhang Y, Barnes SD, Jaichander P, Zheng Y, Hassan M, Malladi VS, Skapek SX, Xu L, Bassel-Duby R, Olson EN, Liu N, Genes Dev. 2019 06 33 11-12 626-640
- Human pancreatic cancer cell exosomes, but not human normal cell exosomes, act as an initiator in cell transformation.
- Stefanius K, Servage K, de Souza Santos M, Gray HF, Toombs JE, Chimalapati S, Kim MS, Malladi VS, Brekken R, Orth K, Elife 2019 05 8
- High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice.
- Peri-Okonny P, Baskin KK, Iwamoto G, Mitchell JH, Smith SA, Kim HK, Szweda LI, Bassel-Duby R, Fujikawa T, Castorena CM, Richardson J, Shelton JM, Ayers C, Berry JD, Malladi VS, Hu MC, Moe OW, Scherer PE, Vongpatanasin W, Circulation 2019 Mar 139 11 1422-1434
- Suppression of Myeloid Cell Arginase Activity leads to Therapeutic Response in a NSCLC Mouse Model by Activating Anti-Tumor Immunity.
- Miret JJ, Kirschmeier P, Koyama S, Zhu M, Li YY, Naito Y, Wu M, Malladi VS, Huang W, Walker W, Palakurthi S, Dranoff G, Hammerman PS, Pecot CV, Wong KK, Akbay EA, J Immunother Cancer 2019 02 7 1 32
- A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.
- Henry GH, Malewska A, Joseph DB, Malladi VS, Lee J, Torrealba J, Mauck RJ, Gahan JC, Raj GV, Roehrborn CG, Hon GC, MacConmara MP, Reese JC, Hutchinson RC, Vezina CM, Strand DW, Cell Rep 2018 12 25 12 3530-3542.e5
- Identification of a multipotent Twist2-expressing cell population in the adult heart.
- Min YL, Jaichander P, Sanchez-Ortiz E, Bezprozvannaya S, Malladi VS, Cui M, Wang Z, Bassel-Duby R, Olson EN, Liu N, Proc. Natl. Acad. Sci. U.S.A. 2018 09 115 36 E8430-E8439
- Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.
- Karaca A, Malladi VR, Zhu Y, Tafaj O, Paltrinieri E, Wu JY, He Q, Bastepe M, Bone 2018 05 110 230-237
- Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes.
- Xi Y, Shi J, Li W, Tanaka K, Allton KL, Richardson D, Li J, Franco HL, Nagari A, Malladi VS, Coletta LD, Simper MS, Keyomarsi K, Shen J, Bedford MT, Shi X, Barton MC, Kraus WL, Li W, Dent SYR, BMC Genomics 2018 02 19 1 150
- Transcription pausing regulates mouse embryonic stem cell differentiation.
- Tastemel M, Gogate AA, Malladi VS, Nguyen K, Mitchell C, Banaszynski LA, Bai X, Stem Cell Res 2017 12 25 250-255
- Dynamic Change of Transcription Pausing through Modulating NELF Protein Stability Regulates Granulocytic Differentiation.
- Liu X, Gogate AA, Tastemel M, Malladi VS, Yao H, Nguyen K, Huang LJ, Bai X, Blood Adv 2017 Aug 1 18 1358-1367