
Available to mentor

As a part of my graduate training in chemical biology and single-molecule biophysics, I resolved the mechanism-of-action and turnover principles of gene regulatory microRNAs at unprecedented spatiotemporal resolution. I combined these skills with training in molecular biology, cell biology and cancer biology to decode the regulatory function and translational potential of small and long non-coding RNAs in DNA damage response and prostate cancer during my postdoctoral fellowship. Leveraging this interdisciplinary training, I made two important discoveries as an independent research investigator – 1) subcellular membrane-less compartments, called biomolecular condensates, are integral components of the cellular stress response and RNA regulation and 2) cellular heterogeneity contributes to distinct cellular decisions in viral infections, stress response and prostate cancer. Building on these findings, my lab seeks to dissect the link between sub-cellular organization, gene regulation and cell signaling in cellular homeostasis and cell fate decisions in health and disease. To address these critical points in stress biology, we use an arsenal of cutting-edge technologies, including single-molecule imaging, super-resolution microscopy, high-throughput imaging, single-cell sequencing, and spatial omics, and combine them with classical approaches.
Since starting my lab in July 2021, my group has discovered that stress response pathways are hyperactive in numerous cancers, including pediatric osteosarcoma and advanced prostate cancer, and represent therapeutically actionable vulnerabilities. On the other hand, we have found that stress response programs are dampened during aging and in neurodegenerative diseases, wherein activating these programs are valuable. My lab working towards understanding foundational mechanisms of stress response and how these programs are disrupted in cancers and degenerative pathologies, whilst working towards identifying methods of therapeutic interventions and accompanying diagnostics.
Sethu Pitchiaya Lab
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Center MemberRogel Cancer Center
The long-term goal of my research program is to understand how mammalian cells respond and adapt to stress and how regulation, aberrations and misappropriation of these foundational processes influence tissue homeostasis, degenerative diseases, and cancer. The ultimate aim is to translate our findings for diagnostic and therapeutic applications. To this end, we use contemporary imaging- and omics-based technologies that we develop and deploy and combine them with classical biochemical and biophysical tools.
Keywords: Stress response and adaptation, Regulation of gene expression, Degenerative diseases, Cancer biology, Single-cell analysis, Single-molecule imaging
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Cho H, Zhang Y, Tien JC, Mannan R, Luo J, Narayanan SP, Mahapatra S, Hu J, Shelley G, Cruz G, Shahine M, Wang L, Su F, Wang R, Cao X, Dhanasekaran SM, Keller ET, Pitchiaya S, Chinnaiyan AM. 2024 Dec 27;PreprintCellular cartography reveals mouse prostate organization and determinants of castration resistance.
DOI:10.1101/2024.12.27.630532 PMID: 39763898 -
Wang X, Qiao Y, Asangani IA, Ateeq B, Poliakov A, Cieślik M, Pitchiaya S, Chakravarthi BVSK, Cao X, Jing X, Wang CX, Apel IJ, Wang R, Ching-Yi Tien J, Juckette KM, Yan W, Jiang H, Wang S, Varambally S, Chinnaiyan AM. Cancer Cell, 2024 Aug 12; 42 (8): 1471Journal ArticleErratum: Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer (Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer (2017) 31(4) (532–548.e7), (S1535610817300600), (10.1016/j.ccell.2017.02.017))
DOI:10.1016/j.ccell.2024.07.009 PMID: 39137731 -
Patel P, Nallandhighal S, Scoville D, Cotta B, Knuth Z, Triner D, Tran L, Udager AM, Rao A, Morgan TM, Palapattu GS, Dadhania V, Pitchiaya S, Salami SS. European Urology Focus, 2024 Jan 1;Journal ArticleSpatial Transcriptomic Profiling to Characterize the Nature of Peripheral- Versus Transition-zone Prostate Cancer
DOI:10.1016/j.euf.2024.11.009 -
Gao G, Sumrall ES, Pitchiaya S, Bitzer M, Alberti S, Walter NG. Nature Reviews Nephrology, 2023 Dec 1; 19 (12): 756 - 770.Journal ArticleBiomolecular condensates in kidney physiology and disease
DOI:10.1038/s41581-023-00767-0 PMID: 37752323 -
Hosono Y, Niknafs YS, Prensner JR, Iyer MK, Dhanasekaran SM, Mehra R, Pitchiaya S, Tien J, Escara-Wilke J, Poliakov A, Chu SC, Saleh S, Sankar K, Su F, Guo S, Qiao Y, Freier SM, Bui HH, Cao X, Malik R, Johnson TM, Beer DG, Feng FY, Zhou W, Chinnaiyan AM. Cell, 2023 Sep 14; 186 (19): 4254 - 4255.Journal ArticleErratum: Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA (Cell (2017) 171(7) (1559–1572.e20), (S0092867417314307), (10.1016/j.cell.2017.11.040))
DOI:10.1016/j.cell.2023.08.025 PMID: 37714137 -
Duran E, Schmidt A, Welty R, Jalihal AP, Pitchiaya S, Walter NG. Wiley Interdisciplinary Reviews: RNA, 2023 Sep 1; 14 (5):Journal ArticleUtilizing functional cell-free extracts to dissect ribonucleoprotein complex biology at single-molecule resolution
DOI:10.1002/wrna.1787 PMID: 37042458 -
Li H, Younger N, Shin HJ, Malik B, Zhao SG, Pitchiaya S, Calvert M, Zhang M, Chang L, Chesner L, Hua J, Li K, Kothari V, Egusa E, Chou J, Das R, Burlingame A, Chinnaiyan AM, Li H, Feng FY. Cancer Research, 2023 Jun 3; 83 (11_Supplement): a027 - a027.Journal ArticleAbstract A027: Identification and characterization of PLUTO-201, a novel lncRNA associated with prostate cancer metastasis
DOI:10.1158/1538-7445.prca2023-a027 -
Berends JE, Dommeti VL, Dudley JN, Carras S, Nam CS, Robinson T, Keller E, Dupree JM, Pitchiaya S. Journal of Urology, 2025 Mar 4; 209 (Supplement 4): e3 - e3.Proceeding / Abstract / PosterMP01-05 Revealing New Paradigms in Male Infertility Through the Lens of Stress-Induced Granules
DOI:10.1097/ju.0000000000003212.05