Varsha Desai Ph.D.

Research Biologist — Division of Systems Biology

Varsha Desai, Ph.D.
(870) 543-7391
NCTRResearch@fda.hhs.gov

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Background

Dr. Varsha Desai studied chemistry at Parle College (affiliated with University of Bombay, India) and graduated with a B.S. degree in 1982. Later, she attended Seth G.S. Medical College (affiliated with University of Bombay, India) to earn an M.S. degree in biochemistry in 1986. There, she investigated the potential of gamma-glutamyl transpeptidase (GGT) enzyme as an early biochemical marker of hepatocellular damage in alcoholics. Dr. Desai further continued her research at Seth G.S. Medical College to demonstrate that hepatic-specificity of the basic isoform of glutathione S-transferase (GST-B1B1) could be used as a diagnostic marker of an early-stage liver metastasis in patients with gastrointestinal tract malignancies and earned a Ph.D. in biochemistry in 1990. Dr. Desai later received training in cell and tissue-culture techniques at Tata Memorial Hospital and Cancer Research Center, Bombay (Mumbai), India, from 1990 to 1993. She continued her research career at NCTR as a research fellow from 1993 to 1997 and then as a postdoctoral fellow of the Oak Ridge Institute for Science and Education from 1997 to 2001. Subsequently, Dr. Desai served as a senior staff fellow from 2001 to 2004, when she was extensively involved in establishing the DNA Microarray Core Facility for the Center for Functional Genomics (later renamed "Personalized Medicine Branch") in NCTR's Division of Systems Biology. Since 2004, Dr. Desai has worked as a research biologist at NCTR. By 2009 she had developed a comprehensive genomics tool for evaluation of mitochondrial function during various drug toxicities. Dr. Desai currently is focused on discovering early predictive preclinical markers of cardiotoxicity induced by an anticancer drug, doxorubicin. During her tenure as a research biologist, Dr. Desai has been recognized for her exemplary research by receiving the “FDA Award of Merit” in 2007 and the “NCTR Director’s Award” in 2012.

Research Interests

There is already substantial evidence indicating mitochondria as a major target of a number of therapeutic drugs and environmental toxins. These insults can impair mitochondrial function through different mechanisms, leading to cellular injury, which can result in organ toxicity and in the worst case, death. Tissues with the highest energy demands, such as the heart, brain, liver, kidney, and skeletal muscle are particularly vulnerable to the defects in mitochondrial activity that can manifest into tissue-specific toxicities or diseases. The primary focus of Dr. Desai’s research is to understand the mechanisms of drug-induced mitochondrial toxicity. Therefore, she developed the first mouse mitochondria-specific expression array (MitoChip) for 542 genes associated with mitochondrial structure and functions at NCTR. With this array she hopes to:

gain insights into the mechanisms underlying various drug-induced toxicities
develop predictive and prognostic biomarkers of toxicity
monitor progression of toxicities and degenerative diseases associated with mitochondrial dysfunction.

In collaborations with academia, this genomics tool generated fresh insights into the novel mechanisms of altered mitochondrial function by anti-HIV drugs, anti-cancer drugs, and environmental toxins in different animal models. This further led to the upgrade of the mouse MitoChip from 542 to 811 genes and development of the rat MitoChip consisting of ~900 genes. The use of MitoChips in different species will advance our understanding of mitochondria-related pathways or genes responsible for interspecies differences in drug-induced toxicities or disease outcomes. Currently, Dr. Desai is developing MitoChips for nonhuman primates and humans. Data generated in rodents, and particularly in nonhuman primates, may help set the stage for the development of drug regimens with greater efficacy and reduced toxicity in humans and help bridge the translational gap between basic laboratory research and clinical studies.

Additionally, Dr. Desai is ambitious about addressing the knowledge gaps in cardiotoxicity induced by doxorubicin (DOX). It is a potent anticancer drug widely used in the treatment of different types of solid tumors and hematological malignancies in children and adults. However, its therapeutic potential and a long-term clinical utility are compromised by a serious side effect of cardiotoxicity that may lead to a life-threatening congestive heart failure. This side effect is a major concern of oncologists as this can occur many years after the cessation of therapy. Dr. Desai therefore developed a DOX-induced chronic cardiotoxicity mouse model that provided crucial knowledge of molecular changes during progression toward cardiotoxicity and identified early predictive biomarkers of cardiotoxicity that may aid in assessment of drug safety or may monitor drug toxicity in clinical practice. Another major risk factor in development of DOX cardiotoxicity is sex-based differential cardiotoxicity. Girls are more susceptible than boys, whereas adult males are more vulnerable than adult females to DOX cardiotoxicity. Dr. Desai advanced her goals in cardiotoxicity by establishing differential cardiotoxicity between the sexes in a chronic cardiotoxicity mouse model, demonstrating that adult male hearts are more susceptible than adult female hearts to DOX toxicity. Furthermore, her study is the first to report that the left atrium is more vulnerable to DOX toxicity than the right atrium or the ventricle. Currently, Dr. Desai is investigating variation in the pharmacokinetics of DOX and cardiac-oxidative stress between the sexes to reveal the mechanisms that may be underlying sex-related differential DOX cardiotoxicity observed in cancer patients.

Professional Societies/National and International Groups

American Aging Association
Full Member
1995 – Present

Society of Toxicology
Full Member
2009 – Present

United Mitochondria Disease Foundation
Full Member
2004 – Present

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Select Publications

Publication titles are linked to text abstracts on PubMed.

Early Metabolomics Changes in Heart and Plasma During Chronic Doxorubicin Treatment in B6C3F1 Mice.
Schnackenberg L., Pence L., Vijay V., Moland C., George N., Cao Z., Yu L., Fuscoe J., Beger R., and Desai V.
J Appl Toxicol. 2016, 36(11):1486-95.

Sex-Related Differential Susceptibility to Doxorubicin-Induced Cardiotoxicity in B6C3F1 Mice.
Jenkins G., Lee T., Moland C., Vijay V., Herman E., Lewis S., Davis K., Muskhelishvili L., Kerr S., Fuscoe J., and Desai V.
Toxicol Appl Pharmacol. 2016, 310:159-174.

Early Transcriptional Changes in Cardiac Mitochondria During Chronic Doxorubicin Exposure and Mitigation by Dexrazoxane in Mice.
Vijay V., Moland C., Han T., Fuscoe J., Lee T., Herman E., Jenkins G., Lewis S., Cummings C., Gao Y., Cao Z., Yu L., and Desai V.
Toxicol Appl Pharmacol. 2016, 295:68-84.

Reproductive Hormone Levels and Differential Mitochondria-Related Oxidative Gene Expression as Potential Mechanisms for Gender Differences in Cardiosensitivity to Doxorubicin in Tumor-Bearing Spontaneously Hypertensive Rats.
Gonzalez Y., Pokrzywinski K., Rosen E., Mog S., Aryal B., Chehab L., Vijay V., Moland C., Desai V., Dickey J., and Rao V.
Cancer Chemother Pharmacol. 2015, 76(3):447-59.

Sexual Dimorphism in the Expression of Mitochondria-Related Genes in Rat Heart at Different Ages.
Vijay V., Han T., Moland C., Kwekel J., Fuscoe J., and Desai V.
PLoS One. 2015, 10(1):e0117047. doi: 10.1371/journal.pone.0117047.

Early Biomarkers of Doxorubicin-Induced Heart Injury in a Mouse Model.
Desai V., Kwekel J., Vijay V., Moland C., Herman E., Lee T., Han T., Lewis S., Davis K., Muskhelishvili L., Kerr S., and Fuscoe J.
Toxicol Appl Pharmacol. 2014, 281(2):221-9.

Development of Doxorubicin-Induced Chronic Cardiotoxicity in the B6C3F1 Mouse Model.
Desai V., Herman E., Moland C., Branham W., Lewis S., Davis K., George N., Lee T., Kerr S., and Fuscoe J.
Toxicol Appl Pharmacol. 2013, 266(1):109-21.

Expression Analysis of Hepatic Mitochondria-Related Genes in Mice Exposed to Acrylamide and Glycidamide.
Lee T., Manjanatha M., Aidoo A., Moland C., Branham W., Fuscoe J., Ali A., and Desai V.
J Toxicol Environ Health A. 2012, 75(6):324-39.

Transgenic Expression of Proximal Tubule Peroxisome Proliferator-Activated Receptor-Alpha in Mice Confers Protection During Acute Kidney Injury.
Li S., Nagothu K., Desai V., Lee T., Branham W., Moland C., Megyesi J., Crew M., and Portilla D.
Kidney Int. 2009, 76(10):1049-62.

Underlying Mitochondrial Dysfunction Triggers Flutamide-Induced Oxidative Liver Injury in a Mouse Model of Idiosyncratic Drug Toxicity.
Kashimshetty R., Desai V., Kale V., Lee T., Moland C., Branham W., New L., Chan E., Younis H., and Boelsterli U.
Toxicol Appl Pharmacol. 2009, 238(2):150-9.

Effect of (+)-Usnic Acid on Mitochondrial Functions as Measured by Mitochondria-Specific Oligonucleotide Microarray in Liver of B6C3F1 Mice.
Joseph A., Lee T., Moland C., Branham W., Fuscoe J., Leakey J., Allaben W., Lewis S., Ali A., and Desai V.
Mitochondrion. 2009, 9(2):149-58.

Effect of Short-Term Exposure to Zidovudine (AZT) on the Expression of Mitochondria-Related Genes in Skeletal Muscle of Neonatal Mice.
Desai V., Lee T., Moland C., Branham W., Von Tungeln L., Beland F., and Fuscoe J.
Mitochondrion. 2009, 9(1):9-16.

Testing for Treatment Effects on Gene Ontology.
Lee T., Desai V., Velasco C., Reis R., and Delongchamp R.
BMC Bioinformatics. 2008, 9 Suppl 9:S20.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)-Induced Expression Profile of Mitochondria-Related Genes in the Mouse Liver.
Desai V., Lee T., Delongchamp R., Leakey J., Lewis S., Lee F., Moland C., Branham W., and Fuscoe J.
Mitochondrion. 2008, 8(2):181-95.

Development of Mitochondria-Specific Mouse Oligonucleotide Microarray and Validation of Data by Real-Time PCR.
Desai V., Lee T., Delongchamp R., Moland C., Branham W., Fuscoe J., and Leakey J.
Mitochondrion. 2007, 7(5):322-9.

Transcriptional Profiling for Understanding the Basis of Mitochondrial Involvement in Disease and Toxicity Using the Mitochondria-Specific MitoChip.
Desai V. and Fuscoe J.
Mutat Res. 2007, 616(1-2):210-2.

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