After completing his M.D., Pravin B. Sehgal, M.D., Ph.D., completed his Ph.D. in the Tamm-Choppin-Darnell labs at the Rockefeller University, where he was on the virology faculty until 1991 (up to the retirement of Dr. Igor Tamm). Then, he moved as full professor at NYMC. Dr. Sehgal had his first NIAID R01 funded in the Spring of 1979. For six years in the latter part of the 80s, he directed the Advanced Virology course for Ph.D. students at Rockefeller University. Also, during those six years, Dr. Sehgal chaperoned the RU institutional Virology seminar series (inviting guest virology speakers from around the country). He has more than 200 publications including for work on Rous sarcoma, rabies, vesicular stomatitis and adenoviruses with a special focus on their molecular biology, transcription and virus-host cell interactions.

In 1980, Dr. Sehgal's lab stumbled on to poly(I).poly(C)-induced human FN-β2. This eventually came to be called the cytokine interleukin-6 (IL-6) in 1988 at a New York Academy of Sciences conference organized in Dec 1988 by Dr. Sehgal and Drs. Gerd Grieninger and Giovanna Tosato. He has been at the forefront of IL-6 research since then (biology, signaling, and cellular effects, STAT transcription factors) and diseases in which IL-6 is implicated (viral and bacterial infections, cancer and pulmonary hypertension).

Three years ago, by serendipity, Dr. Sehgal's lab came across the discovery that IFN-induced MxA structures in the cytoplasm were phase-separated biomolecular condensates. The present work in his lab is to carry out studies on the molecular mechanism of the phase- transitions of Mx proteins (human and murine), and their antiviral effects, especially against SARS-CoV-2.

Education

• M.D., Medicine and Surgery, Seth G.S. Medical College
• Ph.D., Virology and Cell Biology, Rockefeller University

Honors and Awards

• 2012 Endowment Lecturer, Dr. M. V. N. Shrirodkar Endowment, India 
• 2009 Dean's Research Award, New York Medical College
• 1983 Faculty Research Award (declined), American Cancer Society
• 1982 Established Investigator, American Heart Association
• 1982 Career Scientist, The Irma T. Hirschl Foundation
• 1980 Junior Faculty Research Award, American Cancer Society
• 1977 Individual Postdoctoral Fellowship, NCI, NIH
• 1972 Endowment Scholar, The J. N. Tata Endowment
• 1965 Special Scholar, Sir Dorabji Tata Trust
• 1965 The National Merit Scholarship, Government of India

Research

Biomolecular condensates of the interferon-induced antiviral Mx proteins:

• Membraneless organelles (MLOs) in the cytoplasm and nucleus in the form of phase-separated biomolecular condensates are increasingly viewed as critical in regulating diverse cellular functions. We elucidated a paradigm shift over the last 3 years in the field of interferon (IFN)-inducible antiviral Mx-family GTPases. Expression of the “myxovirus resistance proteins” MxA in human cells and its ortholog Mx1 in murine cells is increased 50-100-fold by Type I (IFN-α and –β) and III IFNs (IFN-λ). Human MxA forms cytoplasmic structures, while murine Mx1 forms nuclear bodies. Since 2002, it has been widely thought that human (Hu) MxA is associated with the membraneous smooth endoplasmic reticulum (ER). In a paradigm shift, our recent data showed that HuMxA formed membraneless phase-separated biomolecular condensates in the cytoplasm. The new data bring forward the paradigm that both human MxA and murine Mx1 give rise to phase-separated biomolecular condensates, albeit in different subcellular compartments (cytoplasm vs nucleus), and that differences in the subcellular localization of condensates of different Mx proteins determines the spectrum of their antiviral activity.

Previous research:

• Isolation and assay of human interferon mRNAs and discovery that RNA molecules regulate the stability of human interferon-beta mRNA. This work laid the foundation of methods to clone IFN-β cDNA in 1979. The work on mRNA stability laid the foundation for the subsequent discovery of miRNAs that regulate the stability and translation of eukaryotic mRNA species.
• Discovery of promoter proximal RNA polymerase II pausing derived from studies of the mechanism of action of the mRNA synthesis inhibitor DRB (5,6-dichloro-1-beta-D- ribofuranosylbenzimidazole). DRB was discovered to be reversible inhibitor of mammalian mRNA synthesis. The mechanism of DRB action was discovered to be inhibition of elongation by RNA polymerase II at a promoter-proximal site 100-200 nucleotides downstream. This promoter pausing mechanism has now been extensively validated and its entire biochemistry elucidated. The bottom line: two-thirds of all mammalian genes (including human) have "poised polymerases" already loaded on their transcription units but halted at the DRB-specific pause site (DRB inhibits phosphorylation of CTD of RNA pol II). Thus "transcriptional regulation" for the majority of mammalian genes actually involves the regulated removal of the elongation block at the DRB site.
• The discovery of interleukin-6 (IL-6). In 1980 we were one of two labs that discovered IL-6 as interferon- beta2, the product of a 1.3 kb mRNA in poly(I).poly(C)-induced human fibroblasts. We subsequently cloned and localized the gene for human IL-6 to human chromosome 7, prepared antibodies to the 186-aa protein. In 1986-87 this area of research exploded into the recognition that interferon-beta2 was a multifunctional protein that came to be called IL-6 (in 1988). Subsequently we have participated in all aspects of IL-6 gene expression, molecular biology, biochemistry, clinical implications and functions in collaborations world- wide. I organized the first meeting on IL-6 under the sponsorship of the New York Academy of Sciences in December 1998 at which meeting all the investigators agreed to call this new cytokine IL-6. Indeed, the presence of IL-6 in the host-tumor environment, which we discovered in 1989, is now widely accepted and IL-6 is widely considered to be a driver of cancer cell growth and cancer metastasis.

Publications

• Sehgal PB, Yuan H, Centone A, et. al. "Oral Antiviral Defense: Saliva- and Beverage-like Hypotonicity Dynamically Regulate Formation of Membraneless Biomolecular Condensates of Antiviral Human MxA in Oral Epithelial Cells." Cells, 13(7), (2024) . doi: 10.3390/cells13070590
• Sehgal PB, Yuan H, Jin Y, et. al. "Rapid Reversible Osmoregulation of Cytoplasmic Biomolecular Condensates of Human Interferon-α-Induced Antiviral MxA GTPase." International journal of molecular sciences, 23(21), (2022) . doi: 10.3390/ijms232112739
• Sehgal PB. "Interleukin-6 at the Host-Tumor Interface: STAT3 in Biomolecular Condensates in Cancer Cells." Cells, 11(7), (2022) . doi: 10.3390/cells11071164
• Sehgal PB. "Metastable biomolecular condensates of interferon-inducible antiviral Mx-family GTPases: A paradigm shift in the last three years." Journal of biosciences, 46(3), (2021) . pii: 72
• Sehgal PB, Yuan H, Scott MF, et. al. "Murine GFP-Mx1 forms nuclear condensates and associates with cytoplasmic intermediate filaments: Novel antiviral activity against VSV." The Journal of biological chemistry, 295(52), (2020) 18023-18035. doi: 10.1074/jbc.RA120.015661
• Sehgal PB, Westley J, Lerea KM, et. al. "Biomolecular condensates in cell biology and virology: Phase-separated membraneless organelles (MLOs)." Analytical biochemistry, 597(), (2020) 113691. doi: 10.1016/j.ab.2020.113691
• Davis D, Yuan H, Liang FX, et. al. "Human Antiviral Protein MxA Forms Novel Metastable Membraneless Cytoplasmic Condensates Exhibiting Rapid Reversible Tonicity-Driven Phase Transitions." Journal of virology, 93(22), (2019) . doi: 10.1128/JVI.01014-19

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Professional Service

• 2018- current Member, SOM Admissions Committee
• 1994-1999 Editorial Board J Biol Chem, assorted manuscripts and grants reviewer since 1975
• Mentor to Ph.D. and M.D.-Ph.D. students at Rockefeller and NYMC, and M.S. students at NYMC

Teaching Responsibilities

• Gross Anatomy (since 1995)