Maulik R. Patel, Ph.D.

Assistant Professor

Visit Lab Site

Faculty Appointments
Assistant Professor of Biological Sciences Assistant Professor of Cell and Developmental Biology
Ph.D., Neuroscience, Stanford University, Stanford, CaliforniaB.A., cognitive neuroscience, Grinnell College, Grinnell, Iowa
Office Address
465 21st Ave. South
Nashville, TN 37232
Research Description
Mitochondrial are integral to many aspects of cellular function. We continue to discover new essential roles for mitochondria in cell physiology. Therefore, it is not surprising that mitochondrial dysfunction is associated with an ever-increasing number of human diseases such as cancer, diabetes, infertility, and underlies aging and neurodegenerative disorders. However, despite their importance, fundamental questions regarding mitochondrial biology and disease remain unexplored.

The Patel Lab uses a unique combination of evolutionary framework and functional experimentation to study the biology of mitochondrial DNA (mtDNA). While mtDNA encode genes that are essential for the eukaryotic cell, they can also be viewed as 'selfish' genetic entities trying to maximize their own short- and long-term evolutionary success, often at a great cost to their hosts. The Patel Lab studies the cellular and molecular mechanisms that mtDNA employ to behave 'selfishly' and their consequences on organismal development and physiology. We also study the defense mechanisms that eukaryotic host cells have evolved to detect and curb proliferation of 'selfish' mutant mtDNA, and to deal with their detrimental effects.

mtDNA can behave 'selfishly' in two ways. First, mutant mtDNA variants can directly compete with wildtype mtDNA. Most mutant mtDNA co-exist with wildtype mtDNA in a state of heteroplasmy, and only become pathogenic when their levels exceed a certain threshold. Using the developing germline in C. elegans as a model system, we aim to understand how mutant mtDNA can outcompete their wild type counterparts and can even expand at the expense of host fitness.

Second, mtDNA can behave 'selfishly' by directly competing with the interests of the nuclear genome. Mitochondria are maternally transmitted in most animals including humans. Lack of inheritance through males renders natural selection ineffective at removing mtDNA mutations that are deleterious to males but neutral or beneficial in females. Using powerful genetic tools in Drosophila and Caenorhabditis species, we seek to identify such male-harming mtDNA mutants and characterize their functional consequences. Because decreased male fitness is detrimental for the evolutionary success of the nuclear genome, nuclear-encoded suppressors are predicted to evolve. As with host-pathogen interactions, antagonistic evolution of mtDNA with nuclear suppressors is expected to result in a molecular arms race. We are interested in studying the dynamics of this arms race and its consequences on organismal biology.

Our ultimate aim is to gain fundamental insights into not only how mitochondrial dysfunction causes disease, but to also learn the general evolutionary principles that have the power to explain why and under what circumstances mitochondrial function breaks down. This approach promises to provide a unifying theory to explain origins of many diseases, which are currently viewed as a disparate set of disorders.
Research Keywords
AREAS: Mitochondria, genetics, development, germline, female reproduction and reproductive biology, metabolism, homeostasis, transcription, RNA, evolution, genetic conflict, selfish DNA, positive selection, adaptive evolution, mitochondrial DNA, replication, mtDNA copy number, aging and age related phenotypes, diet and nutrition, stress responses, epigenetics, genetic diseases, mito-nuclear interactions, diabetes. TECHNIQUES: genetic models, molecular biology, knockout models, transgenics, transcriptomics, pharmacology, forward genetic screens, confocal and high resolution live cell imaging, FACS, systems biology, genomics, qPCR and droplet digital PCR, theoretical models, experimental evolution, competition experiments.
Patel MR. Inheritance: Male mtDNA Just Can't Catch a Break. Curr. Biol. 2017 Apr 4/3/2017; 27(7): R264-R266. PMID: 28376332, PII: S0960-9822(17)30228-2, DOI: 10.1016/j.cub.2017.02.057, ISSN: 1879-0445.

Patel MR, Miriyala GK, Littleton AJ, Yang H, Trinh K, Young JM, Kennedy SR, Yamashita YM, Pallanck LJ, Malik HS. A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster. Elife. 2016 Aug 8/2/2016; 5: PMID: 27481326, PMCID: PMC4970871, DOI: 10.7554/eLife.16923, ISSN: 2050-084X.

Gitschlag BL, Kirby CS, Samuels DC, Gangula RD, Mallal SA, Patel MR. Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans. Cell Metab. 2016 Jul 7/12/2016; 24(1): 91-103. PMID: 27411011, PMCID: PMC5287496, PII: S1550-4131(16)30294-7, DOI: 10.1016/j.cmet.2016.06.008, ISSN: 1932-7420.

Chia PH, Patel MR, Wagner OI, Klopfenstein DR, Shen K. Intramolecular regulation of presynaptic scaffold protein SYD-2/liprin-a. Mol. Cell. Neurosci [print-electronic]. 2013 Sep; 56: 76-84. PMID: 23541703, PMCID: PMC3930023, PII: S1044-7431(13)00039-0, DOI: 10.1016/j.mcn.2013.03.004, ISSN: 1095-9327.

Chia PH, Patel MR, Shen K. NAB-1 instructs synapse assembly by linking adhesion molecules and F-actin to active zone proteins. Nat. Neurosci. 2012 Feb; 15(2): 234-42. PMID: 22231427, PMCID: PMC3848868, PII: nn.2991, DOI: 10.1038/nn.2991, ISSN: 1546-1726.

Patel MR, Loo YM, Horner SM, Gale M, Malik HS. Convergent evolution of escape from hepaciviral antagonism in primates. PLoS Biol [print-electronic]. 2012; 10(3): e1001282. PMID: 22427742, PMCID: PMC3302847, PII: PBIOLOGY-D-11-03907, DOI: 10.1371/journal.pbio.1001282, ISSN: 1545-7885.

Patel MR, Emerman M, Malik HS. Paleovirology - ghosts and gifts of viruses past. Curr Opin Virol. 2011 Oct; 1(4): 304-9. PMID: 22003379, PMCID: PMC3190193, DOI: 10.1016/j.coviro.2011.06.007, ISSN: 1879-6265.

Patel MR, Shen K. Neurite extension: starting at the finish line. Cell. 2009 Apr 4/17/2009; 137(2): 207-9. PMID: 19379686, PMCID: PMC3083850, PII: S0092-8674(09)00383-3, DOI: 10.1016/j.cell.2009.04.001, ISSN: 1097-4172.

Patel MR, Shen K. RSY-1 is a local inhibitor of presynaptic assembly in C. elegans. Science. 2009 Mar 3/13/2009; 323(5920): 1500-3. PMID: 19286562, PMCID: PMC3087376, PII: 323/5920/1500, DOI: 10.1126/science.1169025, ISSN: 1095-9203.

Patel MR, Lehrman EK, Poon VY, Crump JG, Zhen M, Bargmann CI, Shen K. Hierarchical assembly of presynaptic components in defined C. elegans synapses. Nat. Neurosci [print-electronic]. 2006 Dec; 9(12): 1488-98. PMID: 17115039, PMCID: PMC3917495, PII: nn1806, DOI: 10.1038/nn1806, ISSN: 1097-6256.

Available Postdoctoral Position Details
Posted: 12/17/2015
Talented postdoctoral candidates are encouraged to apply. Candidates will work on molecular, genetic, cell biological, and evolutionary aspects of mitochondrial DNA dynamics in C. elegans. Candidates seeking to develop their own research program at the intersection of mitochondrial biology and evolution are especially encouraged.