Varsha Desai Ph.D.

Research Biologist — Division of Systems Biology

Varsha Desai, Ph.D.
(870) 543-7121
NCTRResearch@fda.hhs.gov

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Background

Dr. Varsha Desai studied chemistry at Parle College (affiliated with University of Mumbai, India) and graduated with a B.S. degree. Later, she attended Seth Gordhandas Sunderdas (G.S.) Medical College (affiliated with University of Mumbai, India) to earn an M.S. degree in biochemistry. There, she investigated the potential of gamma-glutamyl transpeptidase 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. She continued her research career at FDA’s National Center for Toxicological Research (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 MitoChip, a comprehensive transcriptomics tool for evaluation of mitochondrial function to understand the role of mitochondria in various drug-induced organ toxicities.

For more than a decade, Dr. Desai has focused on discovering early predictive preclinical markers of cardiotoxicity induced by an anticancer drug, doxorubicin (DOX). During her tenure at NCTR, she has published 48 manuscripts in peer-reviewed scientific journals, presented her work at many national and international scientific meetings, and written two invited book chapters describing the use of MitoChip in toxicology. Recently, she was invited by professors from King’s College, London, U.K., to contribute a review chapter on DOX cardiotoxicity and plasma protein markers for the upcoming book, Biomarkers in Toxicology. Dr. Desai has been recognized for her exemplary research by receiving the “FDA Award of Merit” in 2007, the “NCTR Director’s Award” in 2012, and the “FDA Scientific Achievement Award (Excellence in Laboratory Science – Group)” for cardiotoxicity work in 2020.

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 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 insight into the mechanisms underlying various drug-induced organ toxicities.
•   develop predictive and prognostic biomarkers of toxicity.
•   monitor progression of toxicities and degenerative diseases associated with mitochondrial dysfunction.
In collaboration with academia, this transcriptomics 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 MitoChips for the rat (756 genes), nonhuman primates (Rhesus [1507 genes] and Cynomolgus [1417 genes]), and human (1936 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. Data generated in rodents, and more importantly the data generated 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 DOX. It is a potent anticancer drug widely used in the treatment of different types of cancer in children and adults. However, its therapeutic potential and long-term clinical utility are limited 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 within a year or many years after the cessation of therapy. Currently, there is a lack of early biomarkers that can predict the risk of cardiotoxicity after DOX treatment. To address this knowledge gap, Dr. Desai developed a mouse model of DOX-induced chronic cardiotoxicity. This model not only provided novel insights into the mechanisms underlying early- and delayed-onset cardiotoxicity and differential cardiotoxicity between the sexes, but it also allowed identification of early circulating biomarkers (proteins and microRNAs) that may have potential in predicting the risk of cardiotoxicity after DOX treatment. Currently, Dr. Desai is collaborating with oncologists at Arkansas Children’s Hospital, the Center for Drug Evaluation and Research, and investigators at NCTR to examine the clinical potential of candidate preclinical markers in pediatric-cancer patients treated with DOX or other anthracyclines. Furthermore, plasma samples collected from these patients at baseline and various time points during therapy are being analyzed for discovery of novel early-circulating clinical cardiotoxicity biomarkers using a multi-omics approach. Such biomarkers will be beneficial in early decision-making of suitable chemotherapy regimens or pharmacologic interventions to prevent/mitigate adverse cardiovascular outcomes in cancer patients treated with anthracyclines such as DOX.

Professional Societies/National and International Groups

American Aging Association
Full Member
1995 – 2018

Society of Toxicology
Full Member
2009 – Present

United Mitochondria Disease Foundation
Full Member
2004 – 2017

Select Publications

MicroRNA-34a-5p As a Promising Early Circulating Preclinical Biomarker of Doxorubicin-Induced Chronic Cardiotoxicity.
Desai V.G., Vijay V., Lee T., Han T., Moland C.L., Phanavanh B., Herman E.H., Stine K., and Fuscoe J.C.
J Appl Toxicol. 2022, doi: 10.1002/jat.4309. Online ahead of print.

Candidate Early Predictive Plasma Protein Markers of Doxorubicin-Induced Chronic Cardiotoxicity in B6C3F1 Mice.
Desai V., Lee T., Moland C., Vijay V., Han T., Lewis S., Herman E., and Fuscoe J.C.
Toxicol Appl Pharmacol. 2019, 363:164-173.

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.