Raunak Shrestha, PhD
I am the laboratory head for the Shrestha lab - a computational cancer genomics and data science research group at the Center for Prostate Disease Research (CPDR). My research interests fall under the broad categories of cancer genomics, computational biology, systems biology, and machine learning with a special focus on prostate cancer.
I aim to understand a fundamental question - Why do certain individuals with prostate cancer develop aggressive, treatment-refractory disease and acquire resistance to targeted therapies, while others exhibit a favorable response to conventional therapeutic modalities?
The answer to this question lies in understanding the heterogeneous biology of the tumor and its environment, which largely dictates the clinical course and outcomes. I focus on elucidating the drivers of cancer progression and therapeutic resistance, with the goal of advancing personalized medicine and improving clinical outcomes for prostate cancer patients by understanding the complex interplay of the genome, transcriptome, proteome, and epigenome. I address this critical, unmet challenge using an integrated approach that leverages genomics and epigenomics, coupled with advanced techniques in computational biology and machine learning.
I work on the following three major avenues:
- Develop cutting-edge computational genomics and machine learning methods to unravel the complexities of cancer
- Mine, Integrate & Analyze complex multi-modal biological datasets to understand context-specific genome regulation in cancer
- Translate genomic insights to meaningful clinical applications for precision oncology
| Li, H., Melnyk, J. E., Fu, B. X. H., Shrestha, R., Zhang, M., Sjostrom, M., Feng, S., Anderson, J. A., Han, Wanting Chesner, L. N., Shin, H. J., Farsh, T., Suarez, H. J., Nath, S., Chou, J., Das, R., Egusa, E. A., Calvert, M., Kishishita, A., Barpanda, A., Zhu, J., Maheshwari, A., Chen, W. S., Alshalalfa, M., Winters, A., Hua, J. T., Liu, T., Davicioni, E., Wiita, A. P., Stohr, B. A., Siddiqui, J., Huang, B., Small, E. J., Shokat, K. M., Nelson, P., Quigley, D. A., Wasmuth, E. V., Gilbert, L. A., and Feng, F. Y. Genomescale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer. Nature Genetics, 2025. doi: 10.1038/s41588-025-02388-8. URL https://pubmed.ncbi.nlm.nih.gov/41193657 |
| Shrestha, R., Chesner, L. N., Zhang, M., Zhou, S., Foye, A., Lundberg, A., Weinstein, A. S., Sjostrom, M., Zhu, X., Moreno-Rodriguez, T., Li, H., SU2C/PCF West Coast Prostate Cancer Dream Team, Alumkal, J. J., Aggarwal, R., Small, E. J., Lupien, M., Quigley, D. A., and Feng, F. Y. An Atlas of Accessible Chromatin in Advanced Prostate Cancer Reveals the Epigenetic Evolution during Tumor Progression. Cancer Research, 07 2024. ISSN 0008-5472. doi: 10.1158/0008-5472.CAN-24-0890. URL https://pubmed.ncbi.nlm.nih.gov/38990734 |
| Zhao, S. G., Bootsma, M., Zhou, S., Shrestha, R., Moreno-Rodriguez, T., Lundberg, A., Pan, C., Arlidge, C., Hawley, J. R., Foye, A., Weinstein, A. S., Sjöström, M., Zhang, M., Li, H., Chesner, L. N., Rydzewski, N. R., Helzer, K. T., Shi, Y., Bailey, A. M., Zhang, L., Beer, T. M., Thomas, G., Chi, K. N., Gleave, M., Zoubeidi, A., Reiter, R. E., Rettig, M. B., Witte, O., Bose, R., Huang, F. W., Fong, L., Lara, P. N., Evans, C. P., Huang, J., Lynch, M., Dehm, S. M., Lang, J. M., Alumkal, J. J., He, H. H., Wyatt, A. W., Aggarwal, R., Zwart, W., Small, E. J., Quigley, D. A., Lupien, M., Feng, F. Y., and Consortium, W. C. D. T. Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer. Nature Genetics, 07 2024. ISSN 1546-1718. doi: 10.1038/s41588-024-01826-3. URL https://pubmed.ncbi.nlm.nih.gov/39020220 |
| Shrestha, R., Fernandez, M. L., Dawson, A., Hoenisch, J., Volik, S., Lin, Y.-Y., Anderson, S., Kim, H., Haegert, A., Colborne, S., Wong, N., McConeghy, B., Bell, R. H., Brahmbhatt, S., Lee, C.-H., DiMattia, G. E., Le Bihan, S., Morin, G. B., Collins, C. C., and Carey, M. S. Multiomics Characterization of Low-grade Serous Ovarian Carcinoma Identifies Potential Biomarkers of MEK-inhibitor Sensitivity and Therapeutic Vulnerability. Cancer Research, 2021. ISSN 0008-5472. doi: 10.1158/0008-5472.CAN-20-2222. URL https://pubmed.ncbi.nlm.nih.gov/33441310 |
| Shrestha, R., Nabavi, N., Volik, S., Anderson, S., Haegert, A., McConeghy, B., Sar, F., Brahmbhatt, S., Bell, R. H., Le Bihan, S., Wang, Y., Collins, C. C., and Churg, A. Well-Differentiated Papillary Mesothelioma of the Peritoneum is Genetically Distinct from Malignant Mesothelioma. Cancers, 12(6), 06 2020. doi: 10.3390/cancers12061568. URL https://pubmed.ncbi.nlm.nih.gov/32545767 |
| Hodzic, E., Shrestha, R., Malikic, S., Collins, C. C., Litchfield, K., Turajlic, S., and Sahinalp, C. Identification of conserved evolutionary trajectories in tumors. Bioinformatics, 36(Supplement1):i427–i435, 07 2020. ISSN 1367-4803. doi: 10.1093/bioinformatics/btaa453. URL https://pubmed.ncbi.nlm.nih.gov/32657374 |
| Shrestha, R., Nabavi, N., Lin, Y.-Y., Mo, F., Anderson, S., Volik, S., Adomat, H. H., Lin, D., Xue, H., Dong, X., Shukin, R., Bell, R. H., McConeghy, B., Haegert, A., Brahmbhatt, S., Li, E., Oo, H. Z., Hurtado-Coll, A., Fazli, L., Zhou, J., McConnell, Y., McCart, A., Lowy, A., Morin, G. B., Chen, T., Daugaard, M., Sahinalp, S. C., Hach, F., Le Bihan, S., Gleave, M. E., Wang, Y., Churg, A., and Collins, C. C. BAP1 Haploinsufficiency Predicts a Distinct Immunogenic Class of Malignant Peritoneal Mesothelioma. Genome Medicine, 2019. doi: 10.1186/s13073-019-0620-3. URL |
Area of Research
Institution Affiliations
HJF Computational Research Scientist III, in support of Center for Prostate Disease Research (CPDR), Murtha Cancer Center Research Program (MCCRP)
Assistant Professor, Department of Surgery, Uniformed Services University for Health Sciences (USUHS) Adjunct Investigator, Genitourinary Malignancies Branch, National Cancer Institute (NCI)