Update Your ProfileAcademic Title:
Assistant Professor
Primary Appointment:
Microbiology and Immunology
Additional Title:
Assistant Professor
Email:
Location:
660 West Redwood Street Baltimore, MD 21201
Phone (Primary):
(410) 706-4198
Education and Training
2002 Master of Science, Biotechnology, India
2009 PhD, Neuroscience, India
2009- 2012 Post doctorate fellowship , INSERM , France
2012-2018 Post doctorate fellowship, Johns Hopkins, Baltimore, USA
2019-2021 Post doctorate fellowship, University of Maryland, Baltimore, USA
Biosketch
I completed PhD in Neuroscience from National Brain Research Centre(NBRC) India. After my PhD, I accomplished my postdoctoral training in France and USA. My post-doctorate studies were focused on neurodegenerative diseases, especially Parkinson's disease. In 2019, I joined Dr Feldman Ricardo's lab at the University of Maryland, Baltimore as a post doctorate fellow, and in 2023, I was promoted to Assistant Professor.
Research/Clinical Keywords
Neurodegeneration, Parkinson’s disease, dopamine neurons, microglia, pluripotent stem cells, mitochondria, lysosome, alpha synuclein, gene editing
Highlighted Publications
Kumar M, Srikanth MP, Deleidi M, Hallett PJ, Isacson O, Feldman RA. Acid ceramidase involved in pathogenic cascade leading to accumulation of α-synuclein in iPSC model of GBA1-associated Parkinson's disease. Hum Mol Genet. 2023 Feb 8;. doi: 10.1093/hmg/ddad025. [Epub ahead of print] PubMed PMID: 36752535.
Karuppagounder SS, Wang H, Kelly T, Rush R, Nguyen R, Bisen S, Yamashita Y, Sloan N, Dang B, Sigmon A, Lee HW, Marino Lee S, Watkins L, Kim E, Brahmachari S, Kumar M, Werner MH, Dawson TM, Dawson VL. The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson's disease. Sci Transl Med. 2023 Jan 18;15(679):eabp9352. doi: 10.1126/scitranslmed.abp9352. Epub 2023 Jan 18. PubMed PMID: 36652533
Panicker N, Kam TI, Wang H, Neifert S, Chou SC, Kumar M, Brahmachari S, Jhaldiyal A, Hinkle JT, Akkentli F, Mao X, Xu E, Karuppagounder SS, Hsu ET, Kang SU, Pletnikova O, Troncoso J, Dawson VL, Dawson TM. Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson's disease. Neuron. 2022 Aug 3;110(15):2422-2437.e9. doi: 10.1016/j.neuron.2022.05.009. Epub 2022 Jun 1. PubMed PMID: 35654037
Pirooznia SK, Wang H, Panicker N, Kumar M, Neifert S, Dar MA, Lau E, Kang BG, Redding-Ochoa J, Troncoso JC, Dawson VL, Dawson TM. Deubiquitinase CYLD acts as a negative regulator of dopamine neuron survival in Parkinson's disease. Sci Adv. 2022 Apr;8(13):eabh1824. doi: 10.1126/sciadv.abh1824. Epub 2022 Apr 1. PubMed PMID: 35363524
Jo A, Lee Y, Kam TI, Kang SU, Neifert S, Karuppagounder SS, Khang R, Kang H, Park H, Chou SC, Oh S, Jiang H, Swing DA, Ham S, Pirooznia S, Umanah GKE, Mao X, Kumar M, Ko HS, Kang HC, Lee BD, Lee YI, Andrabi SA, Park CH, Lee JY, Kim H, Kim H, Kim H, Cho JW, Paek SH, Na CH, Tessarollo L, Dawson VL, Dawson TM, Shin JH. PARIS farnesylation prevents neurodegeneration in models of Parkinson's disease. Sci Transl Med. 2021 Jul 28;13(604). doi: 10.1126/scitranslmed.aax8891. PubMed PMID: 34321320
Kim JW, Yin X, Jhaldiyal A, Khan MR, Martin I, Xie Z, Perez-Rosello T, Kumar M, Abalde-Atristain L, Xu J, Chen L, Eacker SM, Surmeier DJ, Ingolia NT, Dawson TM, Dawson VL. Defects in mRNA Translation in LRRK2-Mutant hiPSC-Derived Dopaminergic Neurons Lead to Dysregulated Calcium Homeostasis. Cell Stem Cell. 2020 Oct 1;27(4):633-645.e7. doi: 10.1016/j.stem.2020.08.002. Epub 2020 Aug 25. PubMed PMID: 32846140; PubMed Central PMCID: PMC7542555.
Kumar M, Acevedo-Cintrón J, Jhaldiyal A, Wang H, Andrabi SA, Eacker S, Karuppagounder SS, Brahmachari S, Chen R, Kim H, Ko HS, Dawson VL, Dawson TM. Defects in Mitochondrial Biogenesis Drive Mitochondrial Alterations in PARKIN-Deficient Human Dopamine Neurons. Stem Cell Reports. 2020 Sep 8;15(3):629-645. doi: 10.1016/j.stemcr.2020.07.013. Epub 2020 Aug 13. PubMed PMID: 32795422
Brahmachari S, Lee S, Kim S, Yuan C, Karuppagounder SS, Ge P, Shi R, Kim EJ, Liu A, Kim D, Quintin S, Jiang H, Kumar M, Yun SP, Kam TI, Mao X, Lee Y, Swing DA, Tessarollo L, Ko HS, Dawson VL, Dawson TM. Parkin interacting substrate zinc finger protein 746 is a pathological mediator in Parkinson's disease. Brain. 2019 Aug 1;142(8):2380-2401. doi: 10.1093/brain/awz172. PubMed PMID: 31237944
Yun SP, Kam TI, Panicker N, Kim S, Oh Y, Park JS, Kwon SH, Park YJ, Karuppagounder SS, Park H, Kim S, Oh N, Kim NA, Lee S, Brahmachari S, Mao X, Lee JH, Kumar M, An D, Kang SU, Lee Y, Lee KC, Na DH, Kim D, Lee SH, Roschke VV, Liddelow SA, Mari Z, Barres BA, Dawson VL, Lee S, Dawson TM, Ko HS. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nat Med. 2018 Jul;24(7):931-938. doi: 10.1038/s41591-018-0051-5. Epub 2018 Jun 11. PubMed PMID: 29892066
McCall MN, Kim MS, Adil M, Patil AH, Lu Y, Mitchell CJ, Leal-Rojas P, Xu J, Kumar M, Dawson VL, Dawson TM, Baras AS, Rosenberg AZ, Arking DE, Burns KH, Pandey A, Halushka MK. Toward the human cellular microRNAome. Genome Res. 2017 Oct;27(10):1769-1781. doi: 10.1101/gr.222067.117. Epub 2017 Sep 6. PubMed PMID: 28877962
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017 Jan 26;541(7638):481-487. doi: 10.1038/nature21029. Epub 2017 Jan 18. PubMed PMID: 28099414
Karuppagounder SS, Xiong Y, Lee Y, Lawless MC, Kim D, Nordquist E, Martin I, Ge P, Brahmachari S, Jhaldiyal A, Kumar M, Andrabi SA, Dawson TM, Dawson VL. LRRK2 G2019S transgenic mice display increased susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated neurotoxicity. J Chem Neuroanat. 2016 Oct;76(Pt B):90-97. doi: 10.1016/j.jchemneu.2016.01.007. Epub 2016 Jan 22. PubMed PMID: 26808467
Brahmachari S, Ge P, Lee SH, Kim D, Karuppagounder SS, Kumar M, Mao X, Shin JH, Lee Y, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM, Ko HS. Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration. J Clin Invest. 2016 Aug 1;126(8):2970-88. doi: 10.1172/JCI85456. Epub 2016 Jun 27. PubMed PMID: 27348587
Dupuis N, Fafouri A, Bayot A, Kumar M, Lecharpentier T, Ball G, Edwards D, Bernard V, Dournaud P, Drunat S, Vermelle-Andrzejewski M, Vilain C, Abramowicz M, Désir J, Bonaventure J, Gareil N, Boncompain G, Csaba Z, Perez F, Passemard S, Gressens P, El Ghouzzi V. Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans. Hum Mol Genet. 2015 May 15;24(10):2771-83. doi: 10.1093/hmg/ddv038. Epub 2015 Feb 4. PubMed PMID: 25652408.
Kumar M, Csaba Z, Peineau S, Srivastava R, Rasika S, Mani S, Gressens P, El Ghouzzi V. Endogenous cerebellar neurogenesis in adult mice with progressive ataxia. Ann Clin Transl Neurol. 2014 Dec;1(12):968-81. doi: 10.1002/acn3.137. Epub 2014 Nov 4. PubMed PMID: 25574472
Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, Stankowski J, Kim MS, Zhong J, Kumar M, Andrabi SA, Xiong Y, Dickson DW, Wszolek ZK, Pandey A, Dawson TM, Dawson VL. Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Cell. 2014 Apr 10;157(2):472-485. doi: 10.1016/j.cell.2014.01.064. PubMed PMID: 24725412
Srivastava R, Kumar M, Peineau S, Csaba Z, Mani S, Gressens P, El Ghouzzi V. Conditional induction of Math1 specifies embryonic stem cells to cerebellar granule neuron lineage and promotes differentiation into mature granule neurons. Stem Cells. 2013 Apr;31(4):652-65. doi: 10.1002/stem.1295. PubMed PMID: 23225629.
Dupuis N, Lebon S, Kumar M, Drunat S, Graul-Neumann LM, Gressens P, El Ghouzzi V. A novel RAB33B mutation in Smith-McCort dysplasia. Hum Mutat. 2013 Feb;34(2):283-6. doi: 10.1002/humu.22235. Epub 2012 Nov 8. PubMed PMID: 23042644.
Kumar M, Kaushalya SK, Gressens P, Maiti S, Mani S. Optimized derivation and functional characterization of 5-HT neurons from human embryonic stem cells. Stem Cells Dev. 2009 May;18(4):615-27. doi: 10.1089/scd.2008.0181. PubMed PMID: 18800863.
Kumar M, Bagchi B, Gupta SK, Meena AS, Gressens P, Mani S. Neurospheres derived from human embryoid bodies treated with retinoic Acid show an increase in nestin and ngn2 expression that correlates with the proportion of tyrosine hydroxylase-positive cells. Stem Cells Dev. 2007 Aug;16(4):667-81. doi: 10.1089/scd.2006.0115. PubMed PMID: 17784840.
Bagchi B, Kumar M, Mani S. CMV promotor activity during ES cell differentiation: potential insight into embryonic stem cell differentiation. Cell Biol Int. 2006 Jun;30(6):505-13. doi: 10.1016/j.cellbi.2006.01.008. Epub 2006 Mar 6. PubMed PMID: 16621623.
Research Interests
Modeling neurodegenerative disease to study role of pathological alpha-synuclein and mitochondrial defects
Mutation in specific genes causes abnormal protein accumulation and inclusion bodies, which are the common hallmarks of most neurological diseases. Alpha (α)-Synuclein is one of the genes whose mutations cause Parkinson's disease (PD). PD is a neurodegenerative disease with progressive and selective loss of dopamine (DA) neurons. α -Synuclein is a neuronal presynaptic protein, and studies suggest that it has a role in the supply of synaptic vesicles to release neurotransmitters. A point mutation or duplication/triplication of α -Synuclein gene causes a familial form of PD. Under some conditions, α –Synuclein protein forms an α -helical conformation, but in the disease state, it creates a β-sheet-rich structure to form toxic oligomers.
Recent studies in mice and cell lines indicate that accumulation or the loss of protein function affects mitochondrial homeostasis, including bioenergetics and clearance. The mechanism by which a protein's accumulation or loss of function influences the mitochondrial function and dynamics is still unknown. In PD, mitochondrial quality control is compromised and may be one of the major causes of the demise of DA neurons.
Most current research on neurodegenerative disease are based on animal models, over-expression studies or human post-mortem tissue affected with the disease. In all cases, the studies have provided some fundamental advances in understanding neurodegeneration. However, these models have failed to develop an accurate portrait of disease mechanisms happening in humans. This is because the current working models do not fully recapitulate the cellular and molecular events occurring in the human neurons in neurodegenerative disorders. Generating human neurons, glial cells including microglia from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (iPSCs) has the potential to provide a suitable working model for neurodegenerative disorders.
My long-term goals are to study neurodegenerative disorders, including dementias, through the use or development of stem cells and cellular and animal models. My future plans are to incorporate human-induced pluripotent stem cells carrying pathogenic mutations from the patient and use CRISPR/Cas9 gene editing technology to model a variety of pathogenic mutations observed in neurodegenerative diseases, including PARKIN, PINK1, GBA, DJ-1, α-Synuclein and LRRK2 to study the mechanistic basis of neurodegeneration and dementias in human.
Understanding how the mutations promote the accumulation of pathological alpha-synuclein and mitochondrial dysfunction may provide answers to the molecular mechanisms behind neurodegeneration and dementias. Further, I plan to generate 3D midbrain cerebral organoid to study the role of mutant protein in degenerating neurons derived from mutant pluripotent stem cells. The human midbrain organoids contain an organized group of neurons, glia and microglial cells communicating with each other similar to the live human brain. Overall, the study will provide invivo insight into neurodegeneration in humans when a disease is in progress and may bring new avenues to its treatment.
Awards and Affiliations
Professional Society Memberships
2006-2018 International Society for Stem cell Research (ISSCR)
Honors and Awards
2002 Junior Research Fellowship (JRF) Council of Scientific and Industrial Research, Government of India .
2004 Senior Research Fellowship (JRF) Council of Scientific and Industrial Research, Government of India .
2006 New York Stem Cell Foundation (NYSCF) ISSCR Travel Award, Toronto, Ontario.
2007 International Society for Stem Cell Research (ISSCR) Travel Award, Cairns, Australia.
Grants and Contracts
Active Grants:
07/01/2021-06/30/2023 (Co-Inv 40%)PI: Ricardo A. Feldman, UMSOM, New Therapeutic Targets for Prevention an Treatment of GBA1-Associated Parkinson's Disease, Maryland Stem Cells Research Fund
06/01/2022-05/31/2024 (Co-Inv 40%)PI: Ricardo A. Feldman, UMSOM, The role of acid ceramidase in GBA1 associated PD, The Michael J. Fox Foundation for Parkinson's Research
Completed Awards:
2014-2016 (Post-doctoral fellowship, 100%),Human dopaminergic neuronal loss due to Parkin insufficiency:Relevance to Parkinson’s disease, Maryland Stem Cells Research Fund