Dr. Kailash Gulshan

 Our research program is centered on the pathophysiology and treatment of three major conditions: cardiovascular disease, liver disease, and lung cancer. 

Heart disease is still the number one killer in USA and globally. 

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most prevalent liver disease globally. 

Lung cancer is the most deadly cancer causing the most fatalities annually in the U.S. and worldwide. 

Disruption in cholesterol and sphingolipid homeostasis promotes dyslipidemia, leading to type 2 diabetes, atherosclerotic cardiovascular disease (ASCVD), and MASLD. By the year 2030, ~ 40 % of the US population is projected to have some form of CVD. MASLD has also emerged as the most prevalent chronic liver disease, affecting approximately 30% of the global population. Statins are the first choice of anti-dyslipidemia therapy for both CVD and MASLD, but there is still 50% to 70% residual risk even in high-dose statin-treated subjects; in addition, some patients are intolerant of statins. Thus, novel therapeutic targets are needed to tackle these debilitating diseases. High levels of plasma LDL-cholesterol and ceramides are correlated with the severity of ASCVD and MASLD. Sphingomyelin (SM) and ceramide levels are higher in MASLD, and patients with metabolic dysfunction-associated steatohepatitis (MASH) have 20% higher ceramide concentrations versus healthy individuals. Recent studies have shown a link between gut microbiota richness, ceramides, and MASLD. Statins are the first-line treatment for dyslipidemia in CVDnd are also prescribed to MASLD patients, particularly those with pre-existing CVD. Though statins significantly reduced the overall morbidity and mortality, the problem of CVD/MASLD remains unresolved and is showing an upward trend. Thus, there is an unmet need for identification and targeting of new pathways to serve as an adjuvant or stand-alone therapeutic for CVD and MASLD. 

Inflammation is major promoter of CVD, MASLD, as well as lung cancer. The Nlrp3 inflammasome activation of caspases leads to cleavage of N-terminal fragment of GsdmD, which promotes formation of membrane pores and IL-1β release from  macrophages. The long-term goal of my lab is to identify the novel pathways that can be targeted for designing mechanism-based stand-alone or adjuvant therapies to treat and prevent CVD, MASLD, and lung cancer. My lab is focused on dissecting role of signaling lipid Phosphatidylinositol 4,5-bisphosphate (PIP₂), sphingolpid metabolism, inflammasomes, and Gasdermin D (GsdmD) in CVD, MASLD and lung cancer. We employ cutting edge technologies such as Crispr-Cas9 mediated genome editing, bone-marrow transplants, anti-sense oligonucleotide (ASO) mediated generation of mouse models, recombinant adeno-associated virus (rAAV) mediated gene delivery in mice and human cell lines,  mass-spec, Florescence resonance energy transfer (FRET), Surface Plasmon Resonance (SPR), Microscale thermophoresis (MST), Atomic Force Microscopy (AFM), STED, STORM,  Recombinant baculovirus for the expression of recombinant proteins in cultured insect cells (sf9 cells), cell-free proteoliposomal systems to study flip/flop of lipids, Giant Plasma membrane vesicles (GPMVs) isolation/studies, Single cell seq 10X genomics, unbiased lipidomics, RNAseq, gut microbiota profiling,and human induced pluripotent stem cells (hiPSCs)-derived liver/pancreatic organoids.

The lab is actively looking for highly motivated Ph.D candidates, techs, and postdocs to join us in these impactful studies funded by NIH, American Heart Association, and Ohio Cancer Research (OCR).

    Postdoctoral Fellows

1. Dr. Ashutosh Prince: Postdoctoral Fellow, Email:a.prince65@csuohio.edu, Phone: 216-687-2409, Location-SI-310.

2. Dr. Swati Sharma:    Postdoctoral Fellow, Email:s.sharma28@csuohio.edu, Phone: 216-687-2409, Location-SI-310.

   PhD Students

   1. Nilam Bhandari: PhD student, Email:n.bhandari9@vikes.csuohio.edu, Phone: 216-687-2409, Location-SI-310.

   2. Kalash Neupane: PhD student, Email:k.neupane45@vikes.csuohio.edu, Phone: 216-687-2409, Location-SI-310.

   3. Kara Timinski: NHLBI CD-Cavs T32 trainee PhD student, Email:k.timinski@vikes.csuohio.edu, Phone: 216-687-2409, Location-SI-310.

   4. Yavar Shiravand: PhD student, Email:y.shiravand@vikes.csuohio.edu, Phone: 216-687-2409, Location-SI-310.

   Master Students

   1. Malak Tayel: Master's (with thesis) student, Email:m.tayel@vikes.csuohio.edu, Phone: 216-687-2409, Location-SI-310.

   Lab Manager

   Anuradha Modak, Email:a.modak@csuohio.edu, Phone: 216-687-2409, Location-SI-310.

    

   Past Members

   1. Dr. Cynthia A Traughber, Postdoc fellow (moved to biotech industry).

   2. Dr. Mariam R Khan, PhD Student (moved to biotech industry).

    

ORCID link: https://orcid.org/my-orcid?orcid=0000-0002-5598-7370

NCBI bibliography link: https://www.ncbi.nlm.nih.gov/myncbi/kailash.gulshan.3/bibliography/public/

Featured publications:

1. NEDD 4 Pyre-fighters to extinguish inflammation: NEDD4L ubiquitinates Gasdermin D and Gasdermin E to dampen pyroptosis. Gulshan K. Cell Death & Differentiation. 2025 Dec 9. PMID: 41366095
2. Enigmatic functions of ATP8B1: cholestasis, inflammation, phosphoinositide flipping, and cellular homeostasis. Prince A, Traughber CA, Shiravand Y, Bhandari N, Khan MR, Sharma S, Timinski K, Murray KF, Bull LN, Gulshan K*. Cell Cycle. 2025 Oct 14:1-13. PMID: 41084973. (*Corresponding author).
3. ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D. Bhandari N, Prince A, Khan MR, Traughber CA, Neupane K, Lorkowski SW, Brubaker G, Ertugral EG, Kothapalli CR, Dubyak GR, Smith JD, Gulshan K*. PNAS. 2025 Jun 3;122(22):e2502798122. PMID: 40440066. (*Corresponding author).
4. Membrane-bound O-acyltransferase 7 (MBOAT7) shapes lysosomal lipid homeostasis and function to control alcohol-associated liver injury.Varadharajan V, Ramachandiran I, Massey WJ, Jain R, Banerjee R, Horak AJ, McMullen MR, Huang E, Bellar A, Lorkowski SW, Gulshan K, Helsley RN, James I, Pathak V, Dasarathy J, Welch N, Dasarathy S, Streem D, Reizes O, Allende DS, Smith JD, Simcox J, Nagy LE, Brown JM. Elife. 2024 Apr 22;12:RP92243. PMID: 38648183.
5. Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice. Traughber CA, Timinski K, Prince A, Bhandari N, Neupane K, Khan MR, Opoku E, Opoku E, Brubaker G, Nageshwar K, Ertugral EG, Naggareddy P, Kothapalli CR, Smith JD, and Gulshan K*. JAHA. 2024 Apr 16;13(8):e033881. PMID: 38563369. (*Corresponding author).
6. Impavido attenuates inflammation, reduces atherosclerosis, and alters gut microbiota in hyperlipidemic mice. Traughber, CA, Iacano AJ, Khan, MR, Neupane, K, Opoku E, Nunn T, Sangwan N, Hazen SL, Smith JD, and Kailash Gulshan*. iScience. 2023 Mar 20;26(4):106453. doi: 10.1016/j.isci.2023.106453. eCollection 2023 Apr 21. PMID: 37020959. (*Corresponding author).
7. Myeloid-Cell-Specific Role of Gasdermin D in Promoting Lung Cancer Progression in Mice. Traughber, CA, Deshpande, GM, Neupane, K, Bhandari N, Khan, MR, McMullen MR, Shadi S, Opoku E, Muppala S, and Smith JD, and Nagy LE, and Kailash Gulshan*. iScience. 2023 Jan 31;26(2):106076. eCollection 2023 Feb 17. PMID: 36844454. (*Corresponding author).
8. Crosstalk between cholesterol, ABC transporters, and PIP2 in inflammation and atherosclerosis” Advances in Experimental Medicine and Biology. Kailash Gulshan*. 2023; 1422: 353-377. PMID: 36988888 (*Corresponding author).
9. Gasdermin D mediates inflammation-induced defects in reverse cholesterol transport and promotes atherosclerosis. Emmanuel Opoku, C. Alicia Traughber, David Zhang, Amanda J Iacano, Mariam Khan, Juying Han, Jonathan D Smith, and Kailash Gulshan*. Front Cell Dev Biol. 2021 Jul 28;9:715211. PMID: 34395445.(*Corresponding author).
10. Miltefosine increases macrophage cholesterol release and inhibits NLRP3-inflammasome assembly and IL-1β release. Iacano AJ, Lewis H, Hazen JE, Andro H, Smith JD, Kailash Gulshan*. Scientific Report. 2019 Jul 31;9(1):11128. PMID:31366948. (*Corresponding author).
11. V-ATPase (Vacuolar ATPase) Activity Required for ABCA1 (ATP-Binding Cassette Protein A1)-mediated Cholesterol Efflux. Lorkowski SW, Brubaker G, Kailash Gulshan, Smith JD. ATVB. 2018 Nov;38(11):2615-262
12. PI(4,5)P2 Is Translocated by ABCA1 to the Cell Surface Where It Mediates Apolipoprotein A1 Binding and Nascent HDL Assembly. Gulshan K*, Brubaker G, Conger H, Wang S, Zhang R, Hazen SL, Smith JD. Circulation Research. 2016 Sep 16;119(7):827-38. PMID: 27514935. (*Corresponding author).
13. Free-cholesterol-mediated autophagy of ORMDL1 stimulates sphingomyelin biosynthesis. Wang S, Robinet P, Smith JD, Gulshan K*. Autophagy. 2015;11(7):1207-8. PMID: 26042659 (*Corresponding author).
14. Ceramide as a mediator of non-alcoholic Fatty liver disease and associated atherosclerosis. Kasumov T, Li L, Li M, Kailash Gulshan, Kirwan JP, Liu X, Previs S, Willard B, Smith JD, McCullough A. PLoS One. 2015 May 20;10(5)
15. ORMDL orosomucoid-like proteins are degraded by free-cholesterol-loading-induced autophagy. Wang S, Robinet P, Smith JD, Gulshan K*. PNAS. 2015 Mar 24;112(12):3728-33. PMID: 25775599. (*Corresponding author).
16. Role of plasma membrane asymmetry and sphingomyelin in promoting ABCA1 mediated cholesterol efflux (Review). Kailash Gulshan and Smith JD. Clinical Lipidology. 2014 Vol. 9, No. 3, 383-393.
17. Sphingomyelin depletion impairs anionic phospholipid inward translocation and induces   cholesterol efflux. Kailash Gulshan, Brubaker G, Wang S, Hazen SL, Smith JD. JBC. 2013 Dec 27;288(52) :37166-79.
18. ABCA1 Mediates Unfolding of Apolipoprotein-AI N-Terminus on the Cell Surface Before Lipidation and Release of Nascent High-Density Lipoprotein.  Wang S*, Kailash Gulshan*, Brubaker G, Hazen SL, Smith JD. ATVB 2013 Jun;33(6):1197-205 (*Equal First Authors).
19. Proteolytic degradation of the Yap1 transcription factor is regulated by subcellular localization and the E3 ubiquitin ligase Not4. Kailash Gulshan, Thommandru B, Moye-Rowley WS. JBC. 2012 Aug 3;287(32):26796-805.
20. Differential oxidant tolerance determined by the key transcription factor Yap1 is controlled by levels of the Yap1-binding protein,Ybp1. Kailash Gulshan, Lee SS, Moye-Rowley WS. JBC. 2011 Sep 30;286 (39):34071-81.
21. Vacuolar import of phosphatidylcholine requires the ATP-binding cassette transporter Ybt1. Kailash Gulshan, Moye-Rowley WS. Traffic. 2011 Sep;12(9):1257-68.
22. Compartment-specific synthesis of phosphatidylethanolamine is required for normal heavy metal resistance. Kailash Gulshan, Shahi P, Moye-Rowley WS. MBoC. 2010 Feb 1;21(3):443-55.
23. Evidence for the bi-functional nature of mitochondrial phosphatidylserine decarboxylase: role in Pdr3-dependent retrograde regulation of PDR5 expression. Kailash Gulshan, Schmidt JA, Shahi P, Moye-Rowley WS. MCB. 2008 Oct;28(19):5851-64.
24. A nuclear receptor-like pathway regulating multidrug resistance in fungi.  Thakur JK, Arthanari H, Yang F, Pan S, Fan X, Breger J, Frueh D, Kailash Gulshan, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Näär AM. Nature. 2008 Apr 3;452(7187):604-9.
25. Multidrug resistance in fungi. (Review, one of 20 most read articles in Eukaryotic Cell, Nov. 2007) Kailash Gulshan, Moye-Rowley WS. Eukarotic Cell. 2007 Nov;6(11):1933-42.
26. Oxidant-specific folding of Yap1p regulates both transcriptional activation and nuclear localization. Kailash Gulshan, Rovinsky SA, Coleman ST, Moye-Rowley WS. JBC. 2005 Dec 9;280(49):40524-33.

27.  Localization, regulation, and substrate transport properties of Bpt1p, a Saccharomyces cerevisiae MRP-type ABC transporter. Kailash Gulshan Sharma, Mason DL, Liu G, Rea PA, Bachhawat AK, Michaelis S. Eukaryotic Cell.  2002 Jun;1(3):391-400.