Prashant Bhat

MD/PhD student in Division of Biology and Biological Engineering at Caltech through the UCLA-Caltech Medical Scientist Training Program.

Prashant is working to map how sites of RNA processing shape the 3D structures within the nucleus.

 

Undergraduate

Prashant’s interest in pursuing a physician-scientist pathway originated from his undergraduate research experience in Dr. Jennifer Doudna’s RNA biochemistry laboratory at UC Berkeley. During his time there, the lab discovered the biological function of an RNA-mediated enzyme called Cas9 that can be engineered to correct mutations in DNA occurring in human cells. His project focused on the fundamental biology underlying Cascade-Cas3, a complex related to Cas9. 

For Prashant’s senior honors thesis, he developed a biochemical purification method to isolate E. coli Cas3 and established an in vitro DNA degradation assay to reconstitute the CRISPR immune response (Redding et al Cell 2015, Hochstrasser et al PNAS 2014). As of February 2021, Cascade-Cas3 is in clinical trials for the treatment of bacterial urinary tract infections.

Graduate

His current research interests stem directly from patient encounters during medical school where he learned that many patients with cancer, cutaneous disease, or other diseases corresponding to aberrant transcription – have a wide array of mutations in the non-coding regions of their genomes. Furthermore, the nucleus is spatially organized such that DNA, RNA, and protein molecules involved in shared functional and regulatory processes are compartmentalized in three-dimensional (3D) structures. These structures are emerging as a paradigm for gene regulation, a highly complex process that requires the dynamic coordination of hundreds of regulatory factors around precise targets in different cell states. He has contributed to development of a novel method called Split Pool Recognition of Interactions by Tag Extension (SPRITE) that generates high-resolution global maps of RNA and DNA interactions (Quinodoz et al Cell 2017, Quinodoz, Bhat et al biorxiv 2020, Quinodoz, Bhat et al Nature Protocols 2021, in review), which generated a view of nuclear organization around several essential nuclear functions.

Focusing on RNA processing, specifically co-transcriptional splicing, he is now applying SPRITE and genome-wide splicing measurements to study the relationship between compartmentalization of splicing factors and the kinetics of splicing. He is also interested in identifying molecular factors in and around RNA splicing hubs that affect genome-wide splicing of nascent pre-mRNAs. The results of his work aim to address how spatial compartmentalization of biomolecules increases the local concentration of reactants and enzymes such that greater efficiency is achieved in scenarios where rapid responses are required for cell survival.

Prashant’s career goals include pursuing academic medicine, balancing basic science research and clinical practice.

Science and health policy/public outreach

Prashant’s training and experience has also involved exploring the intersection between science, policy, and the public. He was Editor-in-Chief of Berkeley Scientific Journal and a science writer for PLoS before starting medical school. In addition to science writing, he is interested in shaping policy decisions by advocating for continued federal funding of basic science research. To that end, he has participated in face-to-face discussions with advocates and politicians directly involved in policy decisions at the federal level through his involvement in science policy programs in Washington DC and the Dr. Lucy Jones Center for Science and Society. Additionally, as a co-lead of the LGBTQ+ group at the Caltech Center for Inclusion and Diversity, Prashant organizes social and outreach events with the goal to improve all facets of LGBTQ+ life.

Awards and Fellowships:

Prashant graduated with high honors from UC Berkeley and received the second highest overall award (Outstanding Scholar Award) from the Department of Molecular and Cell Biology.

His graduate work is supported by a NIH F30 fellowship (National Cancer Institute), a Chen Graduate Innovator Award, and a Josephine De Karman Dissertation Fellowship.

Basic Science Publications

SPRITE: A genome-wide method to map higher-order 3D spatial interactions in the nucleus using combinatorial split-and-pool barcoding.
Quinodoz, P. Bhat, P. Chovanec, J.W. Jachowicz, N. Ollikainen, E. Detmar, E. Soehalim, and M. Guttman.
Nature Protocols, 2022. *Invited Protocol

Nuclear compartmentalization as a mechanism of quantitative control of gene regulation.
Bhat
, D. Honson, and M. Guttman.
Nature Reviews Molecular and Cell Biology, 2021.

RNA promotes the formation of spatial compartments in the nucleus.
Quinodoz, P. Bhat, N. Ollikainen, J.W. Jachowicz, P. Chovanec, and M. Guttman.
Cell, 2021.

SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses
K. Banerjee*, M. Blanco*, E. Bruce*, D. Honson**, L. Chen**, A. Chow,P. Bhat, N. Ollikainen, S. Quinodoz, C. Loney, J. Thai, Z.D. Miller, A.E. Lin, M.M Schmidt, D.G. Stewart, D. Goldfarb, G. De Lorenzo, S.J. Rihn, R. Voorhees, J.W. Botten, D. Majumdar, and M. Guttman. 
Cell, 2020.

Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus.
Quinodoz, N. Ollikainen, B. Tabak, A. Palla, J.M. Schmidt, E. Detmar, M. Lai, A. Shishkin, P. Bhat, Y. Takei, V. Trinh, E. Aznauryan, P. Russell, C. Cheng, M. Jovanovic, A. Chow, L. Cai, P. McDonel, M. Garber, and M. Guttman. 
Cell, 2018. *F1000 Recommended

Surveillance and processing of foreign DNA by the Escherichia coli CRISPR-Cas system.
Redding, S.H. Sternberg, M. Marshall, B. Gibb, P. Bhat, C.K.Guegler, B. Wiedenheft, J.A. Doudna, & E.C. Greene. 
Cell, 2015.

CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference.
L. Hochstrasser*, D.W. Taylor*, P. Bhat, C.K. Guegler, S.H. Sternberg, E. Nogales, J.A. Doudna.
PNAS, 2014.

Clinical Publications

Patterns of Clinical Progression in Radiorecurrent High-Risk Prostate Cancer.
Levin-Epstein, [and 50 authors, including P. Bhat].
European Urology, 2021.

Comparison of Multimodal Therapies and Outcomes among patients with high- risk prostate adenocarcinoma with adverse clinicopathologic features.
U. Kishan, [and 48 authors, including P. Bhat].
JAMA Network Open, 2021.

Prognostic Significance and Comparative Performance of a Novel PSMA PET/CT-Derived Risk-Stratification Tool for High- and Very High-Risk Prostate Cancer (In review).
A.U. Kishan, [and 50 authors, including P. Bhat].