Positions

Overview

  • Dr. Melkani acquired a Ph.D. degree from Central Drug Research Institute, Lucknow, India (A CSIR premier Drug Institute) & Kumaun University, Nainital, India. For his Ph.D. dissertation, he studied lipoproteins under oxidative stress (in vitro and in vivo) and their cardiovascular implication in humans. After acquiring his Ph.D., he became interested in naturally occurring defense mechanisms involving heat shock proteins, which play a critical role in maintaining protein structure and function during cellular processes and stresses. He drew from his background in oxidative stress in lipoproteins for his postdoctoral position (at the Cal State San Marcos, CA) which focused on how GroEL (heat shock protein HSP-60 analog of E. coli) performs its chaperone function under multiple stress conditions. At the San Diego State University, he then went on to further study the role of chaperones in vivo, particularly in the regulation of cardiac and skeletal muscle as well as in protein folding diseases. For these purposes, he used Drosophila as a model system using genetics, molecular biology, cell biology, cardiac physiology, and gene transfer techniques.

    For his Independent faculty career at SDSU, he used the Drosophila model to explore the mechanism of cardiac failure associated with amyloid accumulation in the cardiomyocytes (referred to as cardiac amyloidosis). He continued his faculty tenure at SDSU before joining the University of Alabama at Birmingham on Oct 1st, 2020, and with multiple collaborations over the years, his research projects are currently supported by three R01 grants. During this tenure, his research group has been at the forefront of developing and using clinically relevant Drosophila models to address the pathophysiological basis of human circadian/metabolic disorders linked to cardiometabolic disease, myofibrillar-myopathies, proteinopathies neuropathies, sleep, and aging disruptions. He also integrates physiological, cell-molecular, genetics, and nutritional approaches to understanding how lifestyle (including, chrono-nutrition, circadian rhythms, and eating/sleeping patterns) and genetic factors act to maintain the structural integrity of cells, tissues, and organs that in turn dictates organismal physiology. Additionally, using strategic collaborations, he applies the findings to higher mammals or even humans to develop therapies for human metabolic and myofibrillar and misfolding protein disorders.

    In addition to his research involvement, he is deeply committed to the academic excellence of undergraduate and graduate students with diverse backgrounds through classroom teaching and lab training. For his university and other services, he has served on various committees and grant review panels. He has also delivered invited talks at various national and international platforms including various universities, institutes, seminars, and conferences. He has reviewed scientific manuscripts for over 35 journals and served/serving on the editorial board of four journals.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2020 Author Correction: Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption (Nature Communications, (2019), 10, 1, (2700), 10.1038/s41467-019-10563-9)Nature Communications.  11. 2020
    2019 Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruptionNature Communications.  10. 2019
    2019 Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases.Annual Review of Nutrition.  39:291-315. 2019
    2019 Suppression of myopathic lamin mutations by muscle-specific activation of AMPK and modulation of downstream signalingHuman Molecular Genetics.  28:351-371. 2019
    2018 Prolonged cross-bridge binding triggers muscle dysfunction in a Drosophila model of myosin-based hypertrophic cardiomyopathy.eLife.  7. 2018
    2018 Increasing autophagy and blocking Nrf2 suppress laminopathy-induced age-dependent cardiac dysfunction and shortened lifespan.Aging Cell.  17:e12747. 2018
    2017 TRiC/CCT chaperonins are essential for maintaining myofibril organization, cardiac physiological rhythm, and lifespanFEBS Letters.  591:3447-3458. 2017
    2017 Time-restricted feeding for prevention and treatment of cardiometabolic disorders 2017
    2017 A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects. 2017
    2016 Huntington's Disease-Induced Cardiac Disorders Affect Multiple Cellular Pathways. 2016
    2016 A Restrictive Cardiomyopathy Mutation in an Invariant Proline at the Myosin Head/Rod Junction Enhances Head Flexibility and Function, Yielding Muscle Defects in Drosophila.Journal of Molecular Biology.  428:2446-2461. 2016
    2016 Using Drosophila as an integrated model to study mild repetitive traumatic brain injury.Scientific Reports.  6:25252. 2016
    2016 The Relay/Converter Interface Influences Hydrolysis of ATP by Skeletal Muscle Myosin II.Journal of Biological Chemistry.  291:1763-1773. 2016
    2015 A Failure to Communicate: MYOSIN RESIDUES INVOLVED IN HYPERTROPHIC CARDIOMYOPATHY AFFECT INTER-DOMAIN INTERACTION.Journal of Biological Chemistry.  290:29270-29280. 2015
    2015 Time-restricted feeding attenuates age-related cardiac decline in Drosophila.Science.  347:1265-1269. 2015
    2014 Mapping interactions between myosin relay and converter domains that power muscle function.Journal of Biological Chemistry.  289:12779-12790. 2014
    2014 Drosophila as a potential model to ameliorate mutant Huntington-mediated cardiac amyloidosis.Rare Diseases.  2:e968003. 2014
    2014 The UNC-45 myosin chaperone: from worms to flies to vertebrates.International Review of Cell and Molecular Biology.  313:103-144. 2014
    2013 Huntington's disease induced cardiac amyloidosis is reversed by modulating protein folding and oxidative stress pathways in the Drosophila heart.PLoS Genetics.  9:e1004024. 2013
    2012 Expression of the inclusion body myopathy 3 mutation in Drosophila depresses myosin function and stability and recapitulates muscle inclusions and weakness. 2012
    2012 Interaction of oxidized chaperonin GroEL with an unfolded protein at low temperatures. 2012
    2012 Alternative relay and converter domains tune native muscle myosin isoform function in Drosophila.Journal of Molecular Biology.  416:543-557. 2012
    2012 Transgenic expression and purification of myosin isoforms using the Drosophila melanogaster indirect flight muscle system.Methods.  56:25-32. 2012
    2011 Two Drosophila myosin transducer mutants with distinct cardiomyopathies have divergent ADP and actin affinities.Journal of Biological Chemistry.  286:28435-28443. 2011
    2011 Drosophila UNC-45 accumulates in embryonic blastoderm and in muscles, and is essential for muscle myosin stability.Journal of Cell Science.  124:699-705. 2011
    2011 The UNC-45 chaperone is critical for establishing myosin-based myofibrillar organization and cardiac contractility in the Drosophila heart model.PLoS ONE.  6:e22579. 2011
    2010 Drosophila UNC-45 prevents heat-induced aggregation of skeletal muscle myosin and facilitates refolding of citrate synthase.Biochemical and Biophysical Research Communications.  396:317-322. 2010
    2010 Mutating the converter-relay interface of Drosophila myosin perturbs ATPase activity, actin motility, myofibril stability and flight ability.Journal of Molecular Biology.  398:625-632. 2010
    2009 Alternative exon 9-encoded relay domains affect more than one communication pathway in the Drosophila myosin head.Journal of Molecular Biology.  389:707-721. 2009
    2008 Divalent cations stabilize GroEL under conditions of oxidative stress.Biochemical and Biophysical Research Communications.  368:625-630. 2008
    2006 Protection of GroEL by its methionine residues against oxidation by hydrogen peroxide.Biochemical and Biophysical Research Communications.  347:534-539. 2006
    2006 alphaB-crystallin maintains skeletal muscle myosin enzymatic activity and prevents its aggregation under heat-shock stress.Journal of Molecular Biology.  358:635-645. 2006
    2005 On the chaperonin activity of GroEL at heat-shock temperature. 2005
    2004 Hydrogen peroxide induces the dissociation of GroEL into monomers that can facilitate the reactivation of oxidatively inactivated rhodanese. 2004
    2004 Oxidized GroEL can function as a chaperonin.Frontiers in Bioscience.  9:724-731. 2004
    2003 The ATPase activity of GroEL is supported at high temperatures by divalent cations that stabilize its structure. 2003
    2002 GroEL interacts transiently with oxidatively inactivated rhodanese facilitating its reactivation.Biochemical and Biophysical Research Communications.  294:893-899. 2002
    2002 Synthesis, conformation and vibrational dynamics of the peptide -Ser-Cys-Lys-Leu-Asp-Phe-, a fragment of apolipoprotein B 2002
    2001 Recurrent strokes--an interesting pedigreeJournal of the Association of Physicians of India.  49:765-766. 2001
    1999 Lipoprotein(a) and coronary heart disease in Indian populationJournal of the Association of Physicians of India.  47:1157-1160. 1999
    1997 Oxidative stress and metabolic control in non-insulin dependent diabetes mellitus 1997
    Time-restricted feeding promotes skeletal muscle function in diet- and genetic-induced obesity through shared and unique pathways

    Research Overview

  • My lab has been at the forefront of developing and using clinically-relevant genetic models (Drosophila melanogaster) to address the pathophysiological basis of human circadian/metabolic disorders linked to cardiometabolic disease, myofibrillar-myopathies, proteinopathies neuropathies, sleep, and aging disruptions. I also integrate physiological, cell-molecular, genetics, genomics, and nutritional approaches to understand how lifestyle (including circadian rhythms, eating/sleeping patterns) and genetic factors act to maintain the structural integrity of cells, tissues, and organs that in turn dictates organismal physiology. Additionally, using strategic collaborations, I apply the findings to higher mammals and humans to develop therapies for human metabolic and myofibrillar and misfolding protein disorders.
    Major Lab Projects:
    1. Circadian Rhythms Disruptions, Cardiometabolic Disorders, Aging, and Their Mitigation using Time-Restricted Feeding, (Currently Funded NIH-NIA R01). See more activities on this project under the research project on my lab webpage.
    2. Cell-molecular Basis of Cardiomyopathies, Neuropathies, and Aging Linked with Protein Misfolding/Aggregation,
    (Currently Funded NIH-NIA MPI R01). See more about previous funding and accomplishments under the research projects on my lab webpage.
    3. Delineate Pathological Pathways Linking Insomnia With Cardiovascular Diseases, (Currently Funded NIH-NHLBI MPI R01). See more about previous funding and accomplishments under the research projects on my lab webpage.
    4. Mutant-Lamin (LMNA) Based Cardiomyopathies, Skeletal Myopathies, and Lipodystrophies: (Previously Funded NIH-NIA R-21 and pending R01). See more on accomplishments of this project under the research projects on my lab webpage.
    5. Machine Learning Approaches for the efficient/automated quantification of Lab assays (Cardiac, Skeletal Muscle, and Sleep/activity data). Description coming soon-------.
  • Teaching Overview

  • Dissertation Committee for Farah Abou Daya (Committee Chair & Mentor) (Graduate Committee Participation)
    Dissertation Committee for Christopher Ramirez Livelo (Committee Chair & Mentor) (Graduate Committee Participation)
    Dissertation Committee for Yiming Guo Livelo (Committee Chair & Mentor) (Graduate Committee Participation)

    Teaching at San Diego State University/UAB

    Bio-567: advanced cell-molecular biology (for 5-semesters) in spring and fall 2014, spring and fall 2015, and fall 2016 (senior undergraduate and graduate-level class).
    MB-610: invited lectures on the molecular basis of aging disease and advanced topics in molecular biology (> 7-semesters from 2013-2020), graduate-level class.
    Biol-797: Graduate research units in molecular cell biology (> 5-semesters, from 2014-2018).
    Bio/Biochem-497 & 499: biology research units (upper division, > 10-semesters, from 2012-2019).
    Bio-299: biology/biochemistry research units (lower division, > 10-semesters, from 2012-2017).
    GBS-798: Non-dissertation Research (2020-current).
    GBS-747 JC: Sleep and Circadian Clocks, serving as a Director from spring 2022
  • Education And Training

  • Doctor of Philosophy in Biochemistry, Kumaun University 2001
  • Master of Science in Organic Chemistry, Kumaun University 1995
  • Bachelor of Science or Mathematics in Chemistry, Kumaun University 1993
  • Full Name

  • Girish Melkani