Mohd Parvez Khan
University of Toledo, University of Pennsylvania, Jawaharlal Nehru University, Aligarh Muslim University, University of Michigan
Research areas: Biochemistry, Genetics and Molecular Biology · Molecular Biology · Bone Metabolism and Diseases · Bone health and osteoporosis research · Medicinal Plant Pharmacodynamics Research
0009-0001-4502-399X
About
Early in my career (Ph.D.), I evaluated the efficacy and mode of action of osteogenic agents and their therapeutic potential in reversing the diabetes-induced osteopenia. Briefly, GTDF (6- C-β-D-glucopyranosyl-(2S, 3S) -(+)- 5,7, 3',4'- tetrahydroxy-dihydro flavonol), was established by our research group as an orally active adiponectin-mimetic and osteoanabolic phytoagent that binds to adiponectin receptors. I investigated the therapeutic potential of this bioactive agent in reversing the diabetes-induced osteopenia in diabetic mice (db/db) model. My study revealed that activating AdipoR1 in bone cells particularly osteoblasts with GTDF completely reverses osteopenia and corrects bone health in type 2 diabetic mice independently of the diabetic phenotype. Next, during my postdoctoral and research associate tenure, I investigated the role of hypoxia-driven pathways, and mitochondrial metabolism in skeletal development and bone mass accrual. I made groundbreaking discoveries regarding the transcription factor Hypoxia Inducible Factor 1a (HIF1) in growth plate development particularly, its role in suppressing mitochondrial respiration and reprogramming bioenergetic metabolism, published in Dev Cell in 2019. I pioneered the notion that energy metabolism, which was once thought to quench the need of metabolites and cellular ATP, can dictate the fate of cells even in hypoxia. I also discovered that mitochondrial metabolism particularly oxidative phosphorylation (OxPhos) and HIF1a signaling crosstalk with each other for governing chondrocyte bioenergetics and growth plate development. My studies further demonstrated that modulation of mitochondrial transcription factor A (TFAM) and HIF1a regulates bone mass accrual and bone quality, thereby uncovering novel mechanistic pathways and therapeutic avenues for metabolic diseases affecting cartilage and bone. In addition, one of my recent works revealed crucial acumens into the role of mitochondrial respiration in cortical bone growth and bone periosteal cell biology. I established the notion that impairing mitochondrial OxPhos can curb the differentiation of periosteal mesenchymal cells into osteoblasts, and that increasing HIF1a activity may mitigate the adverse effects secondary to mitochondrial dysfunction. A paper reporting these findings has been published in JCI Insights 2024. My current work seeks to delineate the molecular interplay between PPARgamma mediated metabolic reprogramming and hypoxia signaling pathways in the pathogenesis of oxidative stress induced skeletal aging, using diverse genetically engineered mouse models and PPARgamma modulators. To elucidate the mechanisms through which PPARgamma regulates HIF1a signaling pathways and OxPhos , thereby reprogramming cellular energy metabolism, I am employing an integrative multi-omics approach. Moreover, I am also testing that whether the metabolic skeletal disorders can be reversed through precise pharmacologic modulation of PPARgamma post-translational modifications targeted for HIF1a activity, specially in reprogramming redox homeostasis. We are testing these hypotheses in the aging skeleton of genetically modified mice using in vivo and ex-vivo approaches in both sexes. This research is particularly significant and innovative because it seeks to define previously unrecognized mechanisms by which the PPARgamma–Hypoxia signaling axis orchestrates skeletal aging.
Employment
- 2023 - Present
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University of Pennsylvania Research Associate/Investigator2022 - 2023
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University of Pennsylvania Post-doctoral research fellow2020 - 2022
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University of Michigan–Ann Arbor Post-doctoral research fellow2016 - 2020
Education
- 2010 - 2016
- 2004 - 2007
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Aligarh Muslim University B.Sc. (Hons)1999 - 2002
Projects & Funding
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HIFs in Absence of PPARg Medical research society2026 - 2027
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Analysis of cortical bone osteocyte phenotype in diabetic and non-diabetic individuals undergoing total hip arthroplasty (THA) Center for Diabetes and Endocrine Research (CeDER), Uni. of Toledo
Publications (43)
- Osteocytes secrete adiponectin and display adipocyte-like phenotype under control of PPARG nuclear receptor Save
- Erythroid precursors regulate local oxygen tension and repair outcomes in the bone marrow niche Save
- A mouse model of Jansen's metaphyseal chondrodysplasia for investigating disease mechanisms and candidate therapeutics. Save
- Pharmacological inhibition of HIF2 protects against bone loss in an experimental model of estrogen deficiency Save
- HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation. Save
- PPARG in osteocytes controls cell bioenergetics and systemic energy metabolism independently of sclerostin levels in circulation. Save
- Regulatory Effect of Osteocytes on Extramedullary and Bone Marrow Adipose Tissue Development and Function. Save
- Erythropoietin and Skeletal Cells CrossTalks in Physiology and Disease Save
- Oxidative phosphorylation in bone cells Save
- Substantially Delayed Maturation of Growth Plate Chondrocytes in “Humanized” PTH1R Mice with the H223R Mutation of Jansen's Disease Save
- Phytoceramides and acylated phytosterol glucosides from Pterospermum acerifolium Willd. Seed coat and their osteogenic activity (vol 81, pg 117, 2012) Save
- Systemic Administration of Recombinant Irisin Accelerates Fracture Healing in Mice Save
- In vivo survival strategies for cellular adaptation to hypoxia: HIF1$α$-dependent suppression of mitochondrial oxygen consumption and decrease of intracellular hypoxia are critical for survival of hypoxic chondrocytes Save
- Hypoxia-inducible factor 2 is a negative regulator of osteoblastogenesis and bone mass accrual Save
- Suppressing mitochondrial respiration is critical for hypoxia tolerance in the fetal growth plate Save
- HIF-2 alpha is Sufficient to Cause Agressive Fibroproliferative Lesions in the Developing Limb Save
- Loss of Hypoxia Inducible Factor-2 Alpha in Mesenchymal Progenitors Increases Bone Mass Accrual and Osteoblastogenesis Save
- Odanacatib Restores Trabecular Bone of Skeletally Mature Female Rabbits With Osteopenia but Induces Brittleness of Cortical Bone: A Comparative Study of the Investigational Drug With PTH, Estrogen, and Alendronate Save
- Detrimental effects of atherogenic and high fat diet on bone and aortic calcification rescued by an isoflavonoid Caviunin $β$-d-glucopyranoside Save
- BMP signaling is required for adult skeletal homeostasis and mediates bone anabolic action of parathyroid hormone Save