
Languages Spoken: English
Sankar Swaminathan, MD has specialized expertise in the treatment of infectious diseases. He is board certified in Internal Medicine and Infectious Diseases. His main clinical focus is in the diagnosis and treatment of infections in immunocompromised patients, including cancer patients and transplant recipients. He has integrated a research program funded by the National Cancer institute on the role of viruses in cancers into his clinical practice.
Clinical Locations
Infectious Diseases, Area E
801-585-2031
Specialties
Board Certification and Academic Information
Academic Departments | Internal Medicine
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Professor Pathology - Adjunct Professor |
Academic Divisions | Infectious Diseases Microbiology and Immunology |
Board Certification | American Board of Internal Medicine American Board of Internal Medicine (Sub: Infectious Disease) American Board of Internal Medicine (Sub: Infectious Disease) |
Sankar Swaminathan, MD has specialized expertise in the treatment of infectious diseases. He is board certified in Internal Medicine and Infectious Diseases. His main clinical focus is in the diagnosis and treatment of infections in immunocompromised patients, including cancer patients and transplant recipients. He has integrated a research program funded by the National Cancer institute on the role of viruses in cancers into his clinical practice.
Academic Locations
Research Statement
The major long-term goal of my research studies is to understand the mechanisms by which human cancer-causing herpesviruses interact with the host cell. We study Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated virus (KSHV). EBV has been identified as a cause of Burkitt’s lymphoma, Hodgkin’s lymphoma, lymphomas in transplant recipients, gastric cancer and nasopharyngeal carcinoma. KSHV causes lymphoma in addition to Kaposi’s sarcoma, a malignancy of the blood vessels. Both of these viruses maintain latent infections in their human host but intermittently lead to uncontrolled cellular proliferation that results in cancer. We apply molecular techniques to identify how specific viral gene products modulate cell functions. We introduce targeted genetic changes into the viral DNA, altering or deleting the gene of interest. Prior to 1990, it was not possible to do this with EBV. We developed techniques which allowed the generation of viable EBV viruses (genetic recombinants) that could be used to determine the role of virtually any EBV gene.
We have applied these and other methods to study a unique EBV gene, known as the SM gene, that regulates not only EBV genes, but also those of the host cell. The SM protein acts by pirating components of the host cell to facilitate expression of EBV genes and also modulates host gene expression. Our most recent research accomplishments include the following:
1) We have shown why the SM gene is essential for EBV replication by using an EBV microarray we developed. Specifically, SM is required for production of EBV DNA polymerase, and therefore for replication of the viral DNA, establishing the potential utility of SM as a therapeutic target for novel treatment modalities.
2) We have shown that SM affects host cell RNA splicing. This effect of EBV on host cell splicing, by altering the levels of signaling in the interferon signaling pathway, is predicted to have an inhibitory effect on IFN gamma signaling. Thus the EBV protein downregulates the host immune response to virus replication at the level of mRNA processing.
3) We have shown that several cellular genes induced by interferon (ISGs) are also induced specifically by SM protein. We have found that three of these cellular proteins potently inhibit growth of tumor cells. We are expressing these proteins in adeno-associated virus (AAV) vectors to determine if they could be used as gene therapy vectors with limited toxicity to normal cells.
4) We discovered and cloned the homolog of the SM gene in KSHV. By specifically deleting the gene from the virus, we showed that this gene is essential for KSHV replication. This work is currently funded by two NIH RO1 grants from the National Cancer Institute and we have been consistently funded by the NIH in the field of gammaherpesvirus research for over 18 years.
Our current research agenda consists of further discovery of the molecular interactions between EBV and KSHV and the host cell. Specifically, we are performing experiments to determine exactly how these RNA binding proteins recognize their target messenger RNAs. By defining the structure and sequence of the target, we will be able to fully understand how the virus modulates cellular gene expression. The second major area of research is to understand the role of the proteins produced by the host cell in response to interferon and viral infection (the ISGs). These proteins are the primary response of the cell to infection, yet surprisingly little is known about their function. By using affinity purification and mass spectroscopy, we are identifying the protein partners of the ISGs to map the pathways that they regulate, and how these protect against virus infection. Understanding the mechanism of action of these proteins has the potential to lead to discovery of protective mechanisms against viral infection.
Board Certification and Academic Information
Academic Departments | Internal Medicine
-
Professor Pathology - Adjunct Professor |
Academic Divisions | Infectious Diseases Microbiology and Immunology |
Board Certification | American Board of Internal Medicine American Board of Internal Medicine (Sub: Infectious Disease) American Board of Internal Medicine (Sub: Infectious Disease) |
Education History
Research Fellow | Beth Israel Hospital, Brigham & Women's Hospital, Dana Farber Cancer Institute Infectious Disease Research Fellow, 1990 |
Research Fellow | Harvard Medical School Microbiology and Molecular Genetics Research Fellow, 1990 |
Fellowship | Beth Israel Hospital, Brigham & Women's Hospital, Dana Farber Cancer Institute Infectious Disease Clinical Fellow, 1988 |
Fellowship | Harvard Medical School Medicine Clinical Fellow, 1988 |
Residency | University of Chicago Medical Center Internal Medicine Resident, 1987 |
Internship | University of Chicago Medical Center Internal Medicine Intern, 1985 |
Professional Medical | Emory University School of Medicine Medicine M.D., 1984 |
Graduate Training | Emory University School of Medicine Microbiology and Immunology M.S., 1982 |
Undergraduate | Harvard College Biochemistry and Molecular Biology, magna cum laude A.B., 1979 |
Selected Publications - Journal Articles
Journal Article
- Harmon KG, Pottinger PS, Baggish AL, Drezner JA, Luks AM, Thompson AA, Swaminathan S (2020). Comorbid Medical Conditions in Young Athletes: Considerations for Preparticipation Guidance During the COVID-19 Pandemic. Sports Health, 12(5), 456-458.
- Verma D, Church TM, Swaminathan S (2020). Epstein-Barr virus co-opts TFIIH component XPB to specifically activate essential viral lytic promoters. Proc Natl Acad Sci U S A, 117(23), 13044-13055.
- Li D, Mosbruger T, Verma D, Swaminathan S (2020). Complex Interactions between Cohesin and CTCF in Regulation of Kaposi's Sarcoma-Associated Herpesvirus Lytic Transcription. J Virol, 94(2).
- Agrawal R, Durupt G, Verma D, Montgomery M, Vieira-de Abreu A, Taylor C, Swaminathan S, Fisher SJ (2019). MicroRNA-7a overexpression in VMH restores the sympathoadrenal response to hypoglycemia. JCI Insight, 4(20).
- Li D, Swaminathan S (2019). Human IFIT proteins inhibit lytic replication of KSHV: A new feed-forward loop in the innate immune system. PLoS Pathog, 15(2), e1007609.
- Sundermann AJ, Clancy CJ, Pasculle AW, Liu G, Cumbie RB, Driscoll E, Ayres A, Donahue L, Pergam SA, Abbo L, Andes DR, Chandrasekar P, Galdys AL, Hanson KE, Marr KA, Mayer J, Mehta S, Morris MI, Perfect J, Revankar SG, Smith B, Swaminathan S, Thompson GR, Varghese M, Vazquez J, Whimbey E, Wingard JR, Nguyen MH (2018). How Clean Is the Linen at My Hospital? The Mucorales on Unclean Linen Discovery Study of Large United States Transplant and Cancer Centers. Clin Infect Dis, 68(5), 850-853.
- Fu W, Verma D, Burton A, Swaminathan S (2019). Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication. J Virol, 93(4).
- Li D, Fu W, Swaminathan S (2018). Continuous DNA replication is required for late gene transcription and maintenance of replication compartments in gammaherpesviruses. PLoS Pathog, 14(5), e1007070.
- Church TM, Verma D, Thompson J, Swaminathan S (2018). Efficient Translation of Epstein-Barr Virus (EBV) DNA Polymerase Contributes to the Enhanced Lytic Replication Phenotype of M81 EBV. J Virol, 92(6).
- Baden LR, Swaminathan S, Angarone M, Blouin G, Camins BC, Casper C, Cooper B, Dubberke ER, Engemann AM, Freifeld AG, Greene JN, Ito JI, Kaul DR, Lustberg ME, Montoya JG, Rolston K, Satyanarayana G, Segal B, Seo SK, Shoham S, Taplitz R, Topal J, Wilson JW, Hoffmann KG, Smith C (2016). Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 14(7), 882-913.
- Verma D, Thompson J, Swaminathan S (2016). Spironolactone blocks Epstein-Barr virus production by inhibiting EBV SM protein function. Proc Natl Acad Sci U S A, 113(13), 3609-14.
- Baglio SR, van Eijndhoven MA, Koppers-Lalic D, Berenguer J, Lougheed SM, Gibbs S, Lveill N, Rinkel RN, Hopmans ES, Swaminathan S, Verkuijlen SA, Scheffer GL, van Kuppeveld FJ, de Gruijl TD, Bultink IE, Jordanova ES, Hackenberg M, Piersma SR, Knol JC, Voskuyl AE, Wurdinger T, Jimnez CR, Middeldorp JM, Pegtel DM (2016). Sensing of latent EBV infection through exosomal transfer of 5'pppRNA. Proc Natl Acad Sci U S A, 113(5), E587-96.
- Thompson J, Verma D, Li D, Mosbruger T, Swaminathan S (2016). Identification and Characterization of the Physiological Gene Targets of the Essential Lytic Replicative Epstein-Barr Virus SM Protein. J Virol, 90(3), 1206-21.
- Verma D, Li DJ, Krueger B, Renne R, Swaminathan S (2015). Identification of the physiological gene targets of the essential lytic replicative Kaposi's sarcoma-associated herpesvirus ORF57 protein. J Virol, 89(3), 1688-702.
- Li DJ, Verma D, Mosbruger T, Swaminathan S (2014). CTCF and Rad21 act as host cell restriction factors for Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication by modulating viral gene transcription. PLoS Pathog, 10(1), e1003880.
Case Report
Letter
Global Impact
News Articles
The Scope & Other Podcasts
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- University of Utah Health Care and Ebola.