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Our Research:

I. Growth hormone and Podocytes

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Glomerular podocytes are terminally differentiated cells that serve as filtration barriers to regulate glomerular permselectivity. These cells are subjected to several insults during metabolic perturbations, and their injury or death manifests in impaired kidney function. 

Our lab is interested in deciphering the molecular events that trigger podocyte injury in diabetic conditions. Particularly during type 1 diabetes, elevated serum Growth hormone (GH) levels are associated with podocyte injury. We investigate how GH induces podocyte injury and contributes to the proteinuric condition.

Selected References: JBC and Cell Death Disease

Selected Publications:

  1. Nishad, R. et al. (2019) “Growth hormone induces NOTCH1 signaling in podocytes and contributes to proteinuria in diabetic nephropathy,” Journal of Biological Chemistry, 294(44), pp. 16109–16122. Available at: https://doi.org/10.1074/jbc.ra119.008966.

  2. Nishad, R., Mukhi, D., Singh, A.K. et al. Growth hormone induces mitotic catastrophe of glomerular podocytes and contributes to proteinuria. Cell Death Dis 12, 342 (2021). https://doi.org/10.1038/s41419-021-03643-6

II. AGEs and Podocytes

Elevated glucose during diabetes contributes to the formation of Advanced glycation end-products (AGEs). AGEs interact with their cognate receptors (RAGE) and elicit signaling events that could contribute to podocyte injury. We longed for an interest in understanding the pathological events triggered in the glomerulus by elevated AGEs. 

Selected Publications:

  1. Nishad, R. et al. (2020) “Activation of notch1 signaling in podocytes by glucose-derived ages contributes to proteinuria,” BMJ Open Diabetes Research & Care, 8(1). Available at: https://doi.org/10.1136/bmjdrc-2020-001203.

  2. Nishad, R. et al. (2021) “Advanced-glycation end-products induce Podocyte injury and contribute to proteinuria,” Frontiers in Medicine, 8. Available at: https://doi.org/10.3389/fmed.2021.685447.

III. HIF1 signaling and Podocytes

Extreme physiological conditions such as hypoxia are presented with an injury to the kidney. Hypoxia-inducible factor 1 (HIF1) transduces intracellular manifestations of hypoxia. Nevertheless, the cellular effects of HIF1 on podocytes are mainly unknown. One of our research interests is to investigate the molecular and cellular events mediated by elevated HIF signaling in podocytes and in the kidney in general. In pathological conditions such as stroke, altered HIF signaling is also implicated in the pathogenesis of proteinuria.

Selected Publications:

  1. Nakuluri, K., Nishad, R., Mukhi, D. et al. Cerebral ischemia induces TRPC6 via HIF1α/ZEB2 axis in the glomerular podocytes and contributes to proteinuria. Sci Rep 9, 17897 (2019). https://doi.org/10.1038/s41598-019-52872-5

  2. Nakuluri K, Mukhi D, Nishad R, Saleem MA, Mungamuri SK, Menon RK, Pasupulati AK. Hypoxia induces ZEB2 in podocytes: Implications in the pathogenesis of proteinuria. J Cell Physiol. 2019 May;234(5):6503-6518. doi: 10.1002/jcp.27387. Epub 2018 Sep 21. PubMed PMID: 30238984

  3. Nakuluri K, Mukhi D, Mungamuri SK, Pasupulati AK. Stabilization of hypoxia-inducible factor 1α by cobalt chloride impairs podocyte morphology and slit-diaphragm function. J Cell Biochem. 2018 Nov 1;. doi: 10.1002/jcb.28041. [Epub ahead of print] PubMed PMID: 30387200

IV. Structural insights of slit-diaphragm proteins

Podocytes possess unique architecture; large nucleus, cell body, and foot processes. Adjacent foot processes are tethered by specialized junctions known as slit-diaphragm (SD). Several proteins constitute the SD including podocin, nephrin, TRPC6, and CD2AP. Our group is interested in elucidating the structural details and molecular evolution of SD proteins. It is interesting to learn how mutations in these proteins alter the architecture of SD and contribute to the pathogenesis of the nephrotic syndrome.

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