Positions

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.  11. 2020
2019 Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases.  Annual Review of Nutrition.  39:291-315. 2019
2017 A Drosophila model of dominant inclusion body myopathy 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects 2017
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-e968003. 2014
2014 The UNC-45 Myosin Chaperone.  International Review of Cell and Molecular Biology.  103-144. 2014
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
A Failure to Communicate.  Journal of Biological Chemistry.  290:29270-29280.
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.
Alternative Exon 9-Encoded Relay Domains Affect More than One Communication Pathway in the Drosophila Myosin Head.  Journal of Molecular Biology.  389:707-721.
Divalent cations stabilize GroEL under conditions of oxidative stress.  Biochemical and Biophysical Research Communications.  368:625-630.
Drosophila UNC-45 accumulates in embryonic blastoderm and in muscles, and is essential for muscle myosin stability.  Journal of Cell Science.  124:699-705.
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.
Expression of the inclusion body myopathy 3 mutation in Drosophila depresses myosin function and stability and recapitulates muscle inclusions and weakness
GroEL interacts transiently with oxidatively inactivated rhodanese facilitating its reactivation.  Biochemical and Biophysical Research Communications.  294:893-899.
Huntington's Disease Induced Cardiac Amyloidosis Is Reversed by Modulating Protein Folding and Oxidative Stress Pathways in the Drosophila Heart.  PLoS Genetics.  9:e1004024-e1004024.
Huntington’s Disease-Induced Cardiac Disorders Affect Multiple Cellular Pathways
Hydrogen peroxide induces the dissociation of GroEL into monomers that can facilitate the reactivation of oxidatively inactivated rhodanese
Increasing autophagy and blocking Nrf2 suppress laminopathy-induced age-dependent cardiac dysfunction and shortened lifespan.  Aging Cell.  17:e12747-e12747.
Interaction of oxidized chaperonin GroEL with an unfolded protein at low temperatures
Lipoprotein(a) and coronary heart disease in Indian population.  Journal of the Association of Physicians of India.  47:1157-1160.
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.
On the chaperonin activity of GroEL at heat-shock temperature
Oxidative stress and metabolic control in non-insulin dependent diabetes mellitus
Oxidized GroEL can function as a chaperonin.  Frontiers in Bioscience.  9:724-724.
Prolonged cross-bridge binding triggers muscle dysfunction in a Drosophila model of myosin-based hypertrophic cardiomyopathy.  eLife.  7.
Protection of GroEL by its methionine residues against oxidation by hydrogen peroxide.  Biochemical and Biophysical Research Communications.  347:534-539.
Recurrent strokes--an interesting pedigree.  Journal of the Association of Physicians of India.  49:765-766.
Suppression of myopathic lamin mutations by muscle-specific activation ofAMPKand modulation of downstream signaling.  Human Molecular Genetics.  28:351-371.
Synthesis, conformation and vibrational dynamics of the peptide -Ser-Cys-Lys-Leu-Asp-Phe-, a fragment of apolipoprotein B
TRiC/CCT chaperonins are essential for maintaining myofibril organization, cardiac physiological rhythm, and lifespan.  FEBS Letters.  591:3447-3458.
The Relay/Converter Interface Influences Hydrolysis of ATP by Skeletal Muscle Myosin II.  Journal of Biological Chemistry.  291:1763-1773.
The UNC-45 Chaperone Is Critical for Establishing Myosin-Based Myofibrillar Organization and Cardiac Contractility in the Drosophila Heart Model.  PLoS ONE.  6:e22579-e22579.
Time-restricted feeding attenuates age-related cardiac decline in Drosophila.  Science.  347:1265-1269.
Time-restricted feeding for prevention and treatment of cardiometabolic disorders
Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption.  Nature Communications.  10.
Two Drosophila Myosin Transducer Mutants with Distinct Cardiomyopathies Have Divergent ADP and Actin Affinities.  Journal of Biological Chemistry.  286:28435-28443.
Using Drosophila as an integrated model to study mild repetitive traumatic brain injury.  Scientific Reports.  6.
αB-Crystallin Maintains Skeletal Muscle Myosin Enzymatic Activity and Prevents its Aggregation under Heat-shock Stress.  Journal of Molecular Biology.  358:635-645.

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:
    2. Cell-molecular Basis of Cardiomyopathies, Neuropathies, and Aging Linked with Protein Misfolding/Aggregation
    3. Delineate Pathological Pathways Linking Insomnia With Cardiovascular Diseases
    4. Mutant-Lamin (LMNA) Based Cardiomyopathies, Skeletal Myopathies, and Lipodystrophies:

    • Principal Investigator On

    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