Shilpa S Dhar, Ph.D.
Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine
About Dr. Shilpa S Dhar
Present Title & Affiliation
Primary Appointment
Assistant Professor, Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston
Faculty, Department of Molecular and Translational Biology, The University of Texas Graduate School of Biomedical Sciences, Houston, TX
Research Interests
Role of histone-modifying enzymes in cancer research. With a mission to accelerate scientific discoveries by supporting and stimulating laboratory research, I seek solutions to the critical problems that apply to fundamental aspects of cancer research, molecular biology, epigenetics and tissue regulation. I am interested in understanding the role of histone modifications. Histone modifications include methylation, acetylation, phosphorylation and ubiquitylation, and play an essential role in regulating gene expression and chromatin architecture, consequently affecting numerous biological processes such as cellular differentiation, development and tumorigenesis. About 30,000 genes are present in human DNA (i.e., the genetic material). The properly controlled expression of these genes is essential for human health. Thus, how genes are regulated or controlled is one of the most fundamental biomedical topics. In this regard, histones are of particular interest, because they are the major DNA partner proteins and because their modifications regulate expression of genes into functional products (e.g., proteins). Histones can undergo various modifications that are exemplified by the addition and removal of small chemical groups, including methyl group, acetyl group and phosphoryl groups. Specifically, the addition of methyl groups on histones is known as histone methylation. This modification is involved in the regulation of more than two-thirds of human genes (>20,000), indicating its tremendously important role for human health via the regulation of human genes linked to cancer development/progression and differentiation of stem cells — stem cells are known as original type of cells with the potential to develop into many different types of cells. This methylation is carried out by methyl-adding enzyme (referred as to methyl “writers”). Since histone modifications are controlled by a cohort of histone-modifying enzymes, I primarily explore the biochemical and biological role of histone-modifying enzymes, especially with an emphasis on histone methyltransferases and demethylases. In parallel, I also study the epigenetic role of these enzymes in the oncogenic events or tumor suppression pathways. TECHNIQUES AND SKILLS: Molecular biology: gene and recombinant DNA cloning, genomic PCR, RT-PCR, cloning full length genes by PCR, sub cloning to expression vectors, DNA sequencing analysis, site directed mutagenesis, CRISPR/CAS9 Mouse Models: Brain-specific conditional Knockout mouse model to study brain tumors Biochemistry: recombinant protein expression and purification, immunodetection and western blot analysis, in vivo and in vitro labeling of proteins with radioactive isotopes and Co-immunoprecipitation, ChIP, ChIP-seq, RNA-Seq, chromosome conformation capture. Cell biology: primary cell culture (neurons), DNA and RNA transfection live cell imaging, cell lysis techniques, immunofluorescence, RNAi (with siRNA, shRNA and lentivirus, retroviral), and proliferation assays. Computer software: Microsoft Word, Excel, and Power Point, Adobe Photoshop, Adobe Illustrator, Microarray analysis, Galaxy, IPA, GSEA, MEV
Education & Training
Degree-Granting Education
| 2005 | Marian University, Fond du Lac, Wisconsin, US, M.S. in Organizational Leadership and Quality |
| 1999 | Gujarat University, Ahmedabad, IN, Ph.D. in Zoology |
| 1994 | Gujarat University, Ahmedabad, IN, M.S. in Zoology (Reproductive Physiology & Endocrinology) |
| 1992 | St. Xavier’s College, Ahmedabad, IN, BS in Zoology / Biochemistry |
Postgraduate Training
| 2010-2013 | Postdoctoral Fellowship, Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas |
| 2006-2008 | Postdoctoral Fellowship, Cell biology and neuroscience, Medical college of Wisconsin, Milwaukee, Wisconsin |
| 2006-2006 | Visiting Scientist, Physiology, Michigan State University, Lansing, Michigan |
Experience & Service
Academic Appointments
Assistant Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2023 - 2024
Instructor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, 2013 - 2021
Research Associate 1, Department of Basic Science Research, Medical College of Wisconsin, Milwaukee, WI, 2008 - 2010
Other Appointments/Responsibilities
Clinical Research Scientist and Geneticist, Bansal Hospital and Safal Fertility Foundation, Ahmedabad, 2001 - 2002
Institutional Committee Activities
Co-Chair for Molecular Translational Biology, Admission, 2024 - 2026
Honors & Awards
| Gujarat Science Congress Medal, Gujarat University | |
| Dr. V.C. Shah Medal, Gujarat University | |
| Project Assistant Award, UGC-DSA | |
| Senior Research Fellow Award, Council of Scientific and Industrial Research (CSIR) | |
| Postdoctoral Travel Award, Medical College of Wisconsin | |
| Fellowship Grant, Center for Cancer Epigenetics | |
| Honorary Member, Advisory Board, Pan Genomics Pvt Ltd | |
| Awesome Job Award, MDACC |
Professional Memberships
Selected Publications
Peer-Reviewed Articles
- Yoshimura K, Fan Y, Yamashita K, Zou G, Wu J, Wang R, Shao S, Scott AW, Jin J, Pizzi MP, Yao X, Brown C, Wang L, Wang L, Gan Q, Waters RE, Yin F, Song S, Dhar SS, Ajani JA. YAP-TEAD-Mediated Tumor Suppression and Immune Modulation of Gastric Adenocarcinoma by HSP90 Inhibition. Cancer Lett None(None):None, 2024. PMID: None.
- Fan Y, Song S, Pizzi MP, Zou G, Vykoukal JV, Yoshimura K, Jin J, Calin GA, Waters RE, Gan Q, Dhar S, Wang L, Hanash S, A Ajani AJ. Exosomal Galectin-3 Promotes Peritoneal Metastases in Gastric Adenocarcinoma via Microenvironment Alterations. iScience None(None):None. e-Pub 2024. PMID: None.
- Sewastjanow-Silva M, Kwiatkowski E, Yamashita K, Abdelhakeem A, Yoshimura K, Vicentini ER, Pizzi MP, Jin J, Fan Y, Zou G, Wang L, Yin F, Dhar SS, Blum Murphy M, Mares JE, Li JJ, Gan Q, Waters RE, Rogers JE, Ajani JA. Three biomarkers (HER2, PD-L1, and microsatellite status) in a large cohort of metastatic gastroesophageal adenocarcinomas: The MD Anderson Cancer Center experience. Int J Cancer None(None):None, 2024. PMID: 38995150.
- Yoshimura K, Zou G, Fan Y, Dai E, Yamashita K, Wu J, Shao S, Scott AW, Jin J, Pizzi MP, Yao X, Brown C, Wang L, Wang R, Li J, Chen H, Wang P, Wang L, Liu B, Zhou J, Gan Q, Waters R, Yin F, Song S, Dhar SS, Ajani JA. CYD0461 Targets SOX9-CDK4 Axis to Suppress Tumor Growth and Enhance Immune Response in Gastric Adenocarcinoma. Cell Report Medicine None(None):None. e-Pub 2024. PMID: None.
- Fan Y, Song S, Li Y, Dhar SS, Jin J, Yoshimura K, Yao X, Wang R, Scott AW, Pizzi MP, Wu J, Ma L, Calin GA, Hanash S, Wang L, Curran M, Ajani JA. Galectin-3 Cooperates with CD47 to Suppress Phagocytosis and T-cell Immunity in Gastric Cancer Peritoneal Metastases. Cancer Res 83(22):3726-3738, 2023. PMID: 37738407.
- Dhar SS, Brown C, Rizvi A, Reed L, Kotla S, Zod C, Abraham J, Abe JI, Rajaram V, Chen K, Lee M. Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation. bioRxiv None(None):None, 2023. PMID: 37961118.
- Napoli M, Wu SJ, Gore BL, Abbas HA, Lee K, Checker R, Dhar S, Rajapakshe K, Tan AC, Lee MG, Coarfa C, Flores ER. ΔNp63 regulates a common landscape of enhancer associated genes in non-small cell lung cancer. Nature Communication 13(1), 2022. PMID: 35105868.
- Alam H, Tang M, Maitituoheti M, Dhar SS, Kumar M, Han CY, Ambati CR, Amin SB, Gu B, Chen TY, Lin YH, Chen J, Muller FL, Putluri N, Flores ER, DeMayo FJ, Baseler L, Rai K, Lee MG. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell 37(4):599-617.e7, 2020. e-Pub 2020. PMID: 32243837.
- Liu Y, Qin S, Chen TY, Lei M, Dhar SS, Ho JC, Dong A, Loppnau P, Li Y, Lee MG, Min J. Structural insights into trans-histone regulation of H3K4 methylation by unique histone H4 binding of MLL3/4. Nat Commun 10(1):36, 2019. e-Pub 2019. PMID: 30604749.
- Alam H, Li N, Dhar SS, Wu SJ, Lv J, Chen K, Flores ER, Baseler L, Lee MG. HP1gamma Promotes Lung Adenocarcinoma by Downregulating the Transcription-Repressive Regulators NCOR2 and ZBTB7A. Cancer Res 78(14):3834-3848, 2018. e-Pub 2018. PMID: 29764865.
- Dhar SS, Zhao D, Lin T, Gu B, Pal K, Wu SJ, Alam H, Lv J, Yun K, Gopalakrishnan V, Flores ER, Northcott PA, Rajaram V, Li W, Shilatifard A, Sillitoe RV, Chen K, Lee MG. MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes. Mol Cell 70(5):825-841.e6, 2018. e-Pub 2018. PMID: 29861161.
- Chen TY, Lee SH, Dhar SS, Lee MG. Protein arginine methyltransferase 7-mediated microRNA-221 repression maintains Oct4, Nanog, and Sox2 levels in mouse embryonic stem cells. J Biol Chem 293(11):3925-3936, 2018. PMID: 29378844.
- Lee SH, Chen TY, Dhar SS, Gu B, Chen K, Kim YZ, Li W, Lee MG. A feedback loop comprising PRMT7 and miR-24-2 interplays with Oct4, Nanog, Klf4 and c-Myc to regulate stemness. Nucleic Acids Res 44(22):10603-10618, 2016. PMID: 27625395.
- Li N, Li Y, Lv J, Zheng X, Wen H, Shen H, Zhu G, Chen TY, Dhar SS, Kan PY, Wang Z, Shiekhattar R, Shi X, Lan F, Chen K, Li W, Li H, Lee MG. ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes. Mol Cell 63(3):470-84, 2016. e-Pub 2016. PMID: 27477906.
- Dhar SS, Lee SH, Chen K, Zhu G, Oh W, Allton K, Gafni O, Kim YZ, Tomoiga AS, Barton MC, Hanna JH, Wang Z, Li W, Lee MG. An essential role for UTX in resolution and activation of bivalent promoters. Nucleic Acids Res 44(8):3659-74, 2016. e-Pub 2016. PMID: 26762983.
- Li N, Dhar SS, Chen TY, Kan PY, Wei Y, Kim JH, Chan CH, Lin HK, Hung MC, Lee MG. JARID1D Is a Suppressor and Prognostic Marker of Prostate Cancer Invasion and Metastasis. Cancer Res 76(4):831-43, 2016. e-Pub 2016. PMID: 26747897.
- Kim JH, Sharma A, Dhar SS, Lee SH, Gu B, Chan CH, Lin HK, Lee MG. UTX and MLL4 coordinately regulate transcriptional programs for cell proliferation and invasiveness in breast cancer cells. Cancer Res 74(6):1705-17, 2014. e-Pub 2014. PMID: 24491801.
- Dhar SS, Alam H, Li N, Wagner KW, Chung J, Ahn YW, Lee MG. Transcriptional repression of histone deacetylase 3 by the histone demethylase KDM2A is coupled to tumorigenicity of lung cancer cells. J Biol Chem 289(11):7483-96, 2014. e-Pub 2014. PMID: 24482232.
- Wagner KW, Alam H, Dhar SS, Giri U, Li N, Wei Y, Giri D, Cascone T, Kim JH, Ye Y, Multani AS, Chan CH, Erez B, Saigal B, Chung J, Lin HK, Wu X, Hung MC, Heymach JV, Lee MG. KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling. J Clin Invest 123(12):5231-46, 2013. e-Pub 2013. PMID: 24200691.
- Johar K, Priya A, Dhar S, Liu Q, Wong-Riley MT. Neuron-specific specificity protein 4 bigenomically regulates the transcription of all mitochondria- and nucleus-encoded cytochrome c oxidase subunit genes in neurons. J Neurochem 127(4):496-508, 2013. e-Pub 2013. PMID: 24032355.
- Dhar SS, Johar K, Wong-Riley MT. Bigenomic transcriptional regulation of all thirteen cytochrome c oxidase subunit genes by specificity protein 1. Open Biol 3(3):120176, 2013. e-Pub 2013. PMID: 23516108.
- Dhar SS, Lee SH, Kan PY, Voigt P, Ma L, Shi X, Reinberg D, Lee MG. Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4. Genes Dev 26(24):2749-62, 2012. PMID: 23249737.
- Dhar SS, Wong-Riley MT. The kinesin superfamily protein KIF17 is regulated by the same transcription factor (NRF-1) as its cargo NR2B in neurons. Biochim Biophys Acta 1813(3):403-11, 2011. e-Pub 2010. PMID: 21172391.
- Kujjo LL, Chang EA, Pereira RJ, Dhar S, Marrero-Rosado B, Sengupta S, Wang H, Cibelli JB, Perez GI. Chemotherapy-induced late transgenerational effects in mice. PLoS One 6(3):e17877, 2011. e-Pub 2011. PMID: 21437292.
- Dhar SS, Wong-Riley MT. Chromosome conformation capture of transcriptional interactions between cytochrome c oxidase genes and genes of glutamatergic synaptic transmission in neurons. J Neurochem 115(3):676-83, 2010. PMID: 21064266.
- Liang HL, Dhar SS, Wong-Riley MT. p38 mitogen-activated protein kinase and calcium channels mediate signaling in depolarization-induced activation of peroxisome proliferator-activated receptor gamma coactivator-1alpha in neurons. J Neurosci Res 88(3):640-9, 2010. PMID: 19774670.
- Dhar SS, Liang HL, Wong-Riley MT. Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons. Biochim Biophys Acta 1793(10):1604-13, 2009. e-Pub 2009. PMID: 19615412.
- Dhar SS, Ongwijitwat S, Wong-Riley MT. Chromosome conformation capture of all 13 genomic Loci in the transcriptional regulation of the multisubunit bigenomic cytochrome C oxidase in neurons. J Biol Chem 284(28):18644-50, 2009. e-Pub 2009. PMID: 19439416.
- Dhar SS, Liang HL, Wong-Riley MT. Nuclear respiratory factor 1 co-regulates AMPA glutamate receptor subunit 2 and cytochrome c oxidase: tight coupling of glutamatergic transmission and energy metabolism in neurons. J Neurochem 108(6):1595-606, 2009. e-Pub 2009. PMID: 19166514.
- Dhar SS, Wong-Riley MT. Coupling of energy metabolism and synaptic transmission at the transcriptional level: role of nuclear respiratory factor 1 in regulating both cytochrome c oxidase and NMDA glutamate receptor subunit genes. J Neurosci 29(2):483-92, 2009. PMID: 19144849.
- Dhar SS, Ongwijitwat S, Wong-Riley MTT. Nuclear respiratory factor 1 regulates all ten nuclear-encoded subunits of cytochrome c oxidase in neurons. J Biol Chem 283(6):3120-3129, 2008. e-Pub 2007. PMID: 18077450.
- Dhar SS, Song S, Huo L, Kumar J, Li Y, Fan Y, Zou G, Wang R, Dai E, Jin J, Scott AW, Shao S, Pizzi MP, Vykoukal JV, Katayama H, Hanash S, Calin GA, Zhang X, Lee MG, Wang Z, Lo Y, Gan Q, Waters RE, Yin F, Wang L, Cheng X, Ajani JA. TRIM28 mediates gastric adenocarcinoma progression and metastases through regulation of Hippo/YAP1 signaling via binding to HNRNPAB. Sci Transl Med None(None):None. PMID: None.
- Dhar SS, Ko KP, Jang J, Brown C, Sillitoe RV, Chen K, Park J, Lee MG. KMT2D acts as an essential determinant for cerebellar granule cell differentiation by programming enhancers at neuronal factor genes. Sci Adv None(None):None. PMID: None.
- Dhar SS, Brown C, Rizvi A, Reed L, Kotla S, Zod C, Abraham J, Abe J, Rajaram V, Chen K, Lee MG. Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of LSD1 and OXPHOS. Cell Rep None(None):None. PMID: None.
- Seo Y, Zhang S, Jang J, Ko K, Kim K, Yuanjian, Huang, Kim D, Kim B, Zou G, Zhang J, Jun S, Chu W, Kirk NA, Hwang YE, Ban YH, Dhar SS, Chan JM, Lee MG, Rudin CM, Park K, Park J. Actin Dysregulation Induces Neuroendocrine Plasticity and Immune Evasion: A Vulnerability of Small Cell Lung Cancer. Nature Medicine None(None):None. PMID: None.
Other Articles
- Napoli, M, Wu, SJ, Gore, BL, Abbas, HA, Lee, K, Checker, R, Dhar, SS, Rajapakshe, K, Aik, CT, Lee, MG, Coarfa, C, Flores, ER Author Correction. Nature communications 13(1), 2022. PMID: 35338160.
- Dhar SS, Lee MG Cancer-epigenetic function of the histone methyltransferase KMT2D and therapeutic opportunities for the treatment of KMT2D-deficient tumors. Oncotarget 12(13):1296-1308, 2021. PMID: 34194626.
- Reed L, Abraham J, Patel S, Dhar SS Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration. MDPI None(Special):None. PMID: None.
Editorials
- Ferrao PT, Rosano L, Poli V, Dhar SS, Lepique AP. Editorial: Women in molecular and cellular oncology. Front Oncol 13(None):1257780, 2023. PMID: 37731644.
- Dhar SS. Editorial: Women in molecular and cellular oncology, volume II: 2022. Front Oncol 13(None):1272365, 2023. PMID: 37727215.
- Dhar SS. Women in Molecular & Cellular Oncology: 2022. Front Oncol None(None):None, 2023. PMID: None.
- Dhar SS, Ferrao PT, Lepique AP, Poli V, Rosano L. Women in Molecular & Cellular Oncology 2021. Frontiers in Oncology None(None):None, 2023. PMID: None.
Grant & Contract Support
| Title: | The Role of histone methyltransferase KMT2D in gastric adenocarcinoma |
| Funding Source: | IRG |
| Role: | PI |
| Title: | Heterozygous KMT2D Loss and Medulloblastoma |
| Funding Source: | NIH/NCI |
| Role: | Co-I |
| Title: | Common Stem Cell Origin of Junctional and Gastric Adenocarcinoma |
| Funding Source: | NIH |
| Role: | Co-I |
| Title: | Modulate innate immune responses to customize therapy in ARID1A- deficient gastric adenocarcinoma |
| Funding Source: | DOD |
| Role: | Co-I |
| Title: | Targeting the Surfaceome in Gastric Cancer for Therapeutic Advantage |
| Funding Source: | DOD |
| Role: | Co-I |
| Title: | Targeting of YAP1 from CAFs in diffuse-type gastric adenocarcinoma |
| Funding Source: | DOD |
| Role: | Co-PI |
| Title: | Gastroesophageal Cancer Patients’ Family Matters |
| Funding Source: | Torrey Coast Foundation |
| Role: | Co-I |
| Title: | Targeting KDM2A in Gastric Adenocarcinoma: A Clinical Approach to Novel Therapeutic Strategies |
| Funding Source: | DOD |
| Role: | PI |
| Title: | Role of histone modifiers in therapy of gastric cancer |
| Funding Source: | Internal Philanthropy Funds |
| Role: | PI |
| Title: | Role of the Histone Modifier KDM2A in Lung Cancer |
| Funding Source: | NIH/NCI |
| Role: | Co-I |
| Title: | ROLE OF THE HISTONE METHYLTRANSFERASE MLL4 IN MEDULLOBLASTOMA |
| Funding Source: | NIH/NCI |
| Role: | Co-I |
| Title: | Discovering Novel Oncoproteins Linked to KMT2D Loss in Gastric Adenocarcinoma |
| Funding Source: | Department of Defense (DOD) |
| Role: | PI |
| Title: | Identifying Novel Oncoproteins Linked to KMT2D Loss in Gastric Adenocarcinoma |
| Funding Source: | NIH/NCI |
| Role: | PI |
| Title: | Investigating role of histone modifiers in Gastric Cancer |
| Funding Source: | NIH/NCI |
| Role: | PI |
Patient Reviews
CV information above last modified November 26, 2024