Anjaneyulu Kowluru, MSc, Ph.D.

Anjaneyulu Kowluru, MSc, Ph.D.

Distinguished Professor and VA Senior Research Career Scientist and Senior Fellow, International Diabetes Federation

Office Location

EACPHS, Suite 3617

Phone

313-577-5490

Email

akowluru@med.wayne.edu

Department

Pharmaceutical Sciences

Research website

https://www.ncbi.nlm.nih.gov/myncbi/1-WSf2Yo9X5wt9/bibliography/public/

Website

https://orcid.org/0000-0003-1700-0077

Anjaneyulu Kowluru, MSc, Ph.D.

Degrees and Certifications

  • B.Sc [Botany, Zoology and Chemistry] Andhra University, India
  • M.Sc [Agricultural Biochemistry] Allahabad University, India
  • Ph.D. [Biochemistry] Indian Institute of Technology, Delhi, India
  • Post-Doctoral Fellow, Brussels Free University School of Medicine, Brussels, Belgium
  • JDRF Fellow, University of Wisconsin School of Medicine, Madison, WI, USA

Positions and Employment

Wayne State University Appointments
  • Distinguished Professor, WSU (2017-)
  • Associate Dean for Research (2023-24)
  • Member, Molecular Therapeutics Program, Karmanos Cancer Institute (2022-)
  • Member, Center for Urban Responses to Environmental Stressors, WSU (2017-)
  • Adjunct Professor, Institute for Environmental and Health Sciences, WSU (2017-)
  • Associate Dean for External Scientific Affairs, College of Pharmacy, WSU (2012-17)
  • Professor (with tenure), Department of Pharmaceutical Sciences, WSU (2001-)
  • Associate Professor, Pharmaceutical Sciences, WSU (1998-2001)

VA Appointments

  • Director, Program for Translational Research in Diabetes, JDD VAMC (2019-)
  • Acting ACOS-R&D, JDD VAMC (2016-17)
  • Deputy ACOS-R&D, JDD VAMC (2015-16)
  • Chair, Research and Development Committee (2012-14)
  • Senior Research Career Scientist, JDD VAMC (2006-)
  • Qualifying PI and Coordinator, Diabetes-REAP, JDD VAMC (2000-05)
  • Research Career Scientist-JDD VAMC (2001-06)
  • Research Scientist and Chief, Beta Cell Biochemistry Laboratory, Middleton VAMC, Madison (1992-98)

Other Appointments

  • Senior Fellow, International Diabetes Federation (2024-)
  • Adjunct Professor, Faculty of Health Sciences, School of Medicine, Curtin University, Perth, Australia (2023-)
  • Member, Elizabeth Weiser Caswell Diabetes Institute, University of Michigan (2019-)
  • Adjunct Professor, School of Biomedical Sciences, Curtin University, Perth, Australia (2013-20)
  • Adjunct Professor, Science and Technology Research Academy, Pune, India (2014-17)
  • Visiting Professor, University of Dundee, Scotland (2007)
  • Visiting Professor, National University of Singapore, Singapore (2002)
  • Visiting Professor (Burroughs Wellcome Trust), University of Keele, Staffordshire, UK (2001)
  • Senior Scientist, Division of Endocrinology, University of Wisconsin School of Medicine, Madison, WI (1991-98)
  • Staff Scientist, Life Sciences Division, Los Alamos National Laboratory, Los Alamos, NM (1984-91)

 

Awards and Honors

  • Junior and Senior Research Fellowships, Council of Scientific and Industrial Research, India [1974-1979]
  • Fellow of the Belgian Institute for Research in Scientific Industry and Agriculture, Belgium [1979-1981]
  • Fellow, Juvenile Diabetes Research Foundation [1982-1984]
  • Coordinator, Diabetes Research Training Program, VA Medical Center, Detroit [2001-2015]
  • Visiting Professor [Burroughs Wellcome Trust], University of Keele, Staffordshire, UK [2001]
  • Visiting Professor, National University of Singapore, Singapore [2001]
  • Board of Governors Charles H. Gershenson Distinguished Faculty Fellow [2004-]
  • Elected Member-WSU Academy of Scholars [2006]
  • Visiting Professor, University of Dundee, Scotland [2006]
  • Bayard D. Catherwood Memorial Lecture, Emory University School of Medicine [2010]
  • Visiting Professor, Curtin University, Perth, Western Australia [2014]
  • Excellence in Healthcare Leadership Award, Curtin University, Perth, Western Australia [2014]
  • Professor, Interdisciplinary Science and Technology Research Academy, University of Pune, India [2014]
  • Distinguished Graduate Faculty Award, Wayne State University [2015]
  • Research Excellence Award, EACPHS, Wayne State University [2017]
  • Distinguished Professor, Wayne State University [2017-]
  • President, Wayne State University Academy of Scholars [2018-19]
  • Adjunct Professor, School of Medicine, Curtin University, Perth, Western Australia (2023-)
  • Senior Fellow, International Diabetes Federation (2024-)

Professional Memberships

Professional Societies (past and present)

  • American Society of Biochemistry and Molecular Biology
  • American Society for Experimental Biology
  • American Diabetes Association
  • American Society for Cell Biology
  • American Physiological Society
  • Association for Research in Vision and Ophthalmology
  • Endocrine Society
  • European Association for the Study of Diabetes
  • European Association for the Study of Diabetes-Islet Study Group
  • American Heart Association
  • Islet Society
  • Alpha Chi Chapter on National Pharmacy Honor Society, Wayne State University
  • Life member, Atherosclerosis Society-India
  • Life Member, Research Society for the Study of Diabetes-India
  • Life Member, Free Radical Society-India
  • Society for Free Radical Biology and Medicine
  • International Society for Eye Research
  • Member, Diversity, Equity and Inclusion Taskforce, American Society of Cell Biology
  • Advisor, American Diabetes Association Islet Biology, Development and Function Interest Group Leadership Team.

Journal Editorial Boards (past and present)

  • Endocrinology 
  • American Journal of Physiology: Endocrinology and Metabolism 
  • Associate Editor, Experimental Diabetes Research 
  • Regional Editor, Recent Patents on Endocrine, Metabolic & Immune Drug Discovery 
  • Biochemical Pharmacology 
  • Islets 
  • Review Editor, Frontiers in Endocrinology 
  • American Journal of Physiology-Endocrinology and Metabolism 
  • Associate Editor-Experimental Diabetes Research
  • Journal of Diabetes Metabolism

Grant Review Panels (past and present)

  • National Institutes of Health 
  • Department of Vetarans Affairs
  • National Science Foundation
  • American Diabetes Association
  • Juvenile Diabetes Research Foundation 
  • Research Grant Council of Hong Kong 
  • Diabetes UK Program 
  • Burroughs Wellcome Trust 
  • Walloon Excellence in Science and Biotechnology, Brussels, Belgium 
  • College of Reviewers for the Canada Research Chairs Program 
  • Fund for Scientific Research-FNRS, Brussels, Belgium 
  • King Abdulaziz City for Science and Technology 
  • Czech Science Foundation 
  • Islet Transplantation Program-JDRF-Australia
  • Wellcome Trust-UK/DBT-Government of India Alliance Program for type-1 diabetes

Areas of Expertise

  • G-protein-mediated signal transduction mechanisms
  • Post-translational modification of proteins, including prenylation, carboxylmethylation, palmitoylation, phosphorylation and dephosphorylation
  • Mechanisms underlying islet beta-cell dysregulation and demise under the duress of metabolic stress and diabetes
  • Proinflammatory cytokine-induced islet beta-cell dysfunction
  • Identification of therapeutic targets for prevention of islet beta-cell dysfunction in diabetes

Primary Research Interest

  • Molecular and cellular mechanisms underlying islet beta-cell function in health and diabetes

Recent Publications

List of publications (past 10 years): From a total of more than 190 peer-revied articles, reviews and book chapters. Not included are more than 325 presentations at local, regional, national and international meetings.  

Kowluru A and Kowluru RA: Phagocyte-like NADPH oxidase [Nox2] in cellular dysfunction in models of glucolipotoxicity and diabetes. Biochemical Pharmacol 88: 275-283, 2014. [PMID 2446291].

Arora DK, Machhadieh B, Matti A, Wadzinski B, Ramanadham S, Kowluru A: High glucose exposure promotes activation of protein phosphatase 2A in rodent islets and INS-1 832/13 cells by increasing the post-translational carboxylmethylation of its catalytic subunit. Endocrinology 155:380-91, 2014. [PMID: 24265448]. 

Kowluru A: Deoxysphingolipids: Beta-cell, beware of these new kids on the block. Diabetes 63:1191-1193, 2014. [PMID: 24651803].

Kowluru RA, Kowluru A, Veluthakal R, Mohammad G, Santos J, Mishra M: Tiam1-Rac1 signaling axis mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia 57: 1047-56, 2014. [PMID: 24554007].

Khadija S, Veluthakal R, Sidarala V, and Kowluru A: Glucotoxic and diabetic conditions induce caspase 6-mediated degradation of nuclear lamin A in human islets, rodent islets and INS-1 832/13 cells. Apoptosis 19:1691-1701, 2014. [PMID: 25292013]. 

Kowluru A: On a sugary-relationship between caspases and lamins. Cell Cycle 13: 3787-3788, 2014. [PMID: 25470565].

Sidarala V, Veluthakal R, Khadija S, and Kowluru A: EHT 1864, a small molecule inhibitor of Ras-related C3 botulinum toxin substrate 1 (Rac1), attenuates glucose-stimulated insulin secretion in pancreatic β-cells. Cellular Signalling 27:1159-1167, 2015. [PMID: 25725286].

Sidarala V, Veluthakal R, Syeda K, Vlaar C, Newsholme P, and Kowluru A: Phagocyte-like NADPH oxidase (Nox2) promotes activation of p38MAPK in pancreatic β-cells under glucotoxic conditions: Evidence for a requisite role of Ras-related C3 botulinum toxin substrate 1 (Rac1). Biochemical Pharmacology 95:301-10, 2015. [PMID: 257252].

Novak M, Leonard MK, Yang HH, Kowluru A, Belkin AM, Kaetzel DM: Metastasis Suppressor NME1 Regulates Melanoma Cell Morphology, Self-Adhesion and Motility via Induction of Fibronectin Expression. Experimental Dermatology 24:455-61, 2015. [PMID: 25808322].

Veluthakal R, Kumar B, Mohammad G, Kowluru A and Renu A. Kowluru Tiam1-Rac1 axis promotes activation of p38 MAP kinase in the development of diabetic retinopathy: Evidence for a requisite role for protein palmitoylation. Cell Physiol Biochem 36:208-20, 2015. [PMID: 25967961].

Kowluru R, Kowluru A and Kumar B: Lipotoxicity augments glucotoxicity-induced mitochondrial damage in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci 56:2985-92, 2015. [PMID: 26024084].

Kowluru RA, Kowluru A, Mishra M, and Kumar B: Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Progress in Retinal and Eye Research 48:40-61, 2015. [PMID: 25975734].

Fang J, Liu M, Sakamoto T, Zhang X, Taatjes D, Jena BP, Kowluru A, Zhang K, Chen X: COPII dependent ER export: a critical component of insulin biogenesis and beta cell ER homeostasis. Mol Endocrinol 29:1156-69, 2015. [PMID: 26083833].

Veluthakal R, Tunduguru R, Arora DK, Sidarala V, Syeda K, Vlaar CP, Thurmond DC, and Kowluru A. Vav2, a guanine nucleotide exchange factor for Ras-related C3 botulinum toxin substrate 1 (Rac1), regulates glucose-stimulated insulin secretion in pancreatic β-cells Diabetologia. 58:2573-81, 2015. [PMID: 26224100].

Kowluru A and Kowluru RA: Protein prenylation in islet β-cell function in health and diabetes: Putting the pieces of the puzzle together. Biochemical Pharmacology 98:363-70, 2015. [PMID: 26215874].

Syeda K, Chen F, Hadden T, Commissaris R, Kowluru A. Nuclear lamins in islet β-cell function. Recent Patents on Endocrine Metabolic and Immune Drug Discovery 9:111-120, 2015. [PMID: 26453024].

Kowluru A. A lack of glue misplaces Rab27A to cause islet dysfunction in diabetes. J Pathol 238:375-377, 2016. [PMID: 26575346].

Zhang X, Damacharla D, Ma D, Qi Y, Tagett R, Draghici S, Kowluru A, and Yi Z: Quantitative mass spectrometric identification of protein interaction partners of the catalytic subunit of protein phosphatase 2A in pancreatic β-cells. Molecular and Cellular Endocrinology 424:1-11, 2016. [PMID: 26780722].

Veluthakal R, Sidarala V, Kowluru A: NSC23766, a known inhibitor of Tiam1-Rac1 signaling module, prevents the onset of type 1 diabetes in the NOD mouse model. Cell Physiol Biochem 39:760-767, 2016. [PMID: 27467102].

Kowluru RA, Mishra M, Kowluru A, Kumar B: hyperlipidemia and the development of diabetic retinopathy: Comparison between type1 and type 2 animal models. Metabolism 65:1570-1581, 2016. [PMID: 27621192].

Veluthakal R, Arora DK, Goalstone ML, Kowluru RA and Kowluru A: Metabolic stress induces caspase-3 mediated degradation and inactivation of farnesyl and geranylgeranyl transferase activities in pancreatic β-cells. Cell Physiol Biochem 39:2110-2120, 2016. [PMID: 27802439].

Sidarala V and Kowluru A: The regulatory roles of mitogen-activated protein kinase (MAPK) pathways in health and diabetes: Lessons learnt from the pancreatic beta-cell Recent Patents on Endocrine, Metabolic and Immune Drug Discovery 10:76-84, 2016. [PMID: 27779078].

Kowluru A. Tiam1/Vav2-Rac1 axis: A tug-of-war between islet function and dysfunction. Biochemical Pharmacology 132:9-17, 2017. [PMID: 28202288].

Sidarala V and Kowluru A. Exposure to chronic hyperglycemic conditions results in Ras-related C3 botulinum toxin substrate 1 [Rac1]-mediated activation of p53 and ATM kinase in pancreatic β-cells. Apoptosis 22: 597-607, 2017. [PMID: 28220272].

Kowluru A. Inappropriate movement of Rac1 contributes to glucotoxicity of the islet β-cell. Cell Cycle 16:1387-1388, 2017. [PMID: 28723259].

Kowluru A. Role of G-proteins in islet function in health and diabetes. Diabetes, Obesity and Metabolism 19 [supplement 1] 63-75, 2017. [PMID: 28880478].

Baidwan S, Chekuri A, Kowluru A. Glucotoxicity promotes aberrant activation and mislocalization of Ras-related C3 botulinum toxin substrate 1 [Rac1] and metabolic dysfunction in pancreatic islet β-cells: Reversal of such metabolic defects by metformin. Apoptosis, 22:1380-1393, 2017. [PMID: 288287705].

Syeda GK, Kowluru A. Pharmacological inhibition of prenylation promotes caspase 3 activation, lamin B degradation and induces loss in metabolic cell viability in pancreatic beta-cells. Cell Physiol Biochem 43: 1052-1063, 2017. [PMID: 28968609].

Khan S, Kowluru A. Inhibition of deacetylases attenuates lipid accumulation and caspase 3 activation in pancreatic beta cells under the duress of glucolipotoxicity; Potential roles of CD36 activity. Biochem Biophys Res Commun. 495:2221-2226, 2018. [PMID: 29274335].

Duraisamy AJ, Mishra M, Kowluru A, Kowluru RA. Epigenetics and regulation of oxidative stress in diabetic retinopathy. Invest Ophthalmol Vis Sci. 59:4831-4840, 2018. [PMID: 30347077].

Kowluru A, Kowluru R. RACking up ceramide-induced islet β-cell dysfunction. Biochemical Pharmacology, Biochem Pharmacol. 154:161-169, 2018 [PMID: 29715450].

Damacharla D, Thamilselvan V, Zhang X, Mestareehi A, Yi Z, Kowluru A. Quantitative proteomics reveals novel interaction partners of Rac1 in pancreatic β-cells: Evidence for increased interaction with Rac1 under glucotoxic conditions. Molecular and Cellular Endocrinology, 494:1-15, 2019 [PMID: 31202817].

Mohammad G, Duraisamy AJ, Kowluru A, Kowluru RA. Functional regulation of Rac1 and the development of diabetic retinopathy. Mol Neurobiol. 56:8643-8655, 2019. [PMID: 31300985].

Sahajpal N, Kowluru A, Kowluru RA. The regulatory role of Rac1, a small molecular weight GTPase, in the development of diabetic retinopathy. J Clin Med, in press 2019. [PMID: 31277234].

Qi Q, Seyome B, Msallaty Z, Mallisho A, Caruso M, Damacharla D, Ma D, Al-janabi W, Tagett R, Alharbi M, Calme G, Draghici S, Abou-Samra A, Kowluru A, Zhang X, Yi Z. Global kinome profiling reveals abnormal active kinases in human skeletal muscle from obes insulin resistant participants. J Clin Endo Metab 105:1-16, 2019. [PMID: 31652310] .

Kowluru A. GPCRs, G proreins and impacts on beta-cell function. Comprehensive Physiology (Handbook of Physiology series). 10:453-490, 2020. [PMID 32163203]

Kowluru A. Potential roles of PP2A-Rac1 signaling axis in pancreatic beta cell dysfunction under metabolic stress: Progress and potential. Biochemical Pharmacology. 180: 114138, 2020. [PMID: 32634437]

Thamilselvan V, Gamage S, Chundru A, Kowluru A. P-Rex1, a guanine nucleotide exchange factor for Rac1, regulates glucose-and mastoparan-induced insulin secretion. Cellular Physiology and Biochemistry. 54:1218-1230, 2020. [PMID:33347743]

Kowluru A. Oxidative stress as a mediator of cytokine-induced dysfunction of the islet beta cell: The Known knowns and known unknowns. Invited review for publication in a thematic issue in Metabolites titled “Islet Inflammation and Metabolic Homeostasis”. In press (2020) https://doi.org/10.3390/metabo10120480 [PMID: 33255484]

Thamilselvan V, Kowluru A. Paradoxical regulation of glucose-induced Rac1 activation and insulin secretion by LyGDI in pancreatic β-cells. Small GTPases, 12:114-121, 2021. [PMID: 31267831].

Kowluru A. Roles of GTP and Rho GTPases in islet beta-cell function and dysfunction. Invited review to be published in a thematic issue titled “The Rho family of small GTPases in physiology and disease” in Small GTPases 12:323-335, 2021 [PMID: 32867592]

Chundru SA, Hajrali A, Hajli M, Gleason N, Gamage S, Kowluru A. RhoG-Rac1 signaling pathway mediates metabolic dysfunction of the pancreatic beta-cells under chronic hyperglycemic conditions. Cell Physiol Biochem. 55:180-192, 2021 [PMID: 33851799] 

Mestareehi A, Zhang X, Seyoum B, Msallaty Z, Mallisho A, Burghardt KJ, Kowluru A, Yi Z. Metformin Increases Protein Phosphatase 2A Activity In Primary Human Skeletal Muscle Cells Derived from Lean Healthy Participants. J Diabetes Res (2021) doi: 10.1155/2021/9979234. eCollection 2021. [PMID: 34368369]

Hainan L, Nguyen H, Meda Venkata SP, Koh JI, Kowluru A, Li L, Rossi N, Wang J. A novel role of G protein-coupled receptor 35 in the regulation of endothelial cell function and blood pressure. Hypertension (2021) doi: 10.1161/HYPERTENSIONAHA.120.15423. [PMID: 34275335]

Gamage S, Hali M, Kowluru A: CARD9 mediates glucose-stimulated insulin secretion in pancreatic beta cells. Biochemical Pharmacol (2021) doi: 10.1016/j.bcp.2021.114670. [PMID: 34233162].

Kowluru A: Multiple guanine nucleotide exchange factors mediate glucose induced Rac1 activation and insulin secretion: Is it precise regulatory control or a case of two peas from the same pod? ACS Pharmacology&Translational Science 4:1702-1704, 2021 [PMID: 34661084]

Kowluru A and Gleason N: Underappreciated roles for Guanine Nucleotide Dissociation Inhibitors (GDIs) in Cellular Function: Lessons Learned from G Protein Signaling in the Pancreatic Beta Cell. Biochemical Pharmacol (2022). DOI: 10.1016/j.bcp.2021.114886 [PMID: 34968495]

Gamage S, Hali M, Chen F, and Kowluru A. CARD9 mediates pancreatic islet beta-cell dysfunction under the duress of chronic hyperglycemia. Cellular Physiology and Biochemistry 56:120-137, 2022. [PMID: 35362297]

Hali M, Wadzinski B, Kowluru A. Alpha4 contributes to the metabolic dysfunction of the pancreatic beta cell under metabolic stress. Mol. Cell. Endocrinol. 557:111754. doi: 10.1016/j.mce.2022.111754. [PMID: 35987388].

Kowluru A, Gamage S, Hali M, Gleason N: Hyperglycemic conditions promote Rac1-mediated Serine536 phosphorylation of p65 subunit of NFκB (RelA) in pancreatic beta cells. Cellular Physiology and Biochemistry 56:367-381, 2022 [PMID: 35981264]

Venkata SPN, Li H, Xu L, Koh JY, Nguyen H, Minijares M, Li C, Kowluru A, Milligan G, Wang JM. Inhibition of GPR39 Restores Defects in Endothelial Cell-Mediated Angiogenesis under the Duress of Chronic Hyperglycemia: Evidence for Novel Regulatory Roles of the Sonic Hedgehog Signaling Axis. Proc Natl Acad Sci (USA)  120(1):e2208541120. doi: 10.1073/pnas.2208541120 [PMID: 36574661]

Kowluru A:Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1? Biochem Pharmacol. 218:115889. doi: 10.1016/j.bcp.2023.115889. 2023.

Gleason N, Williams C, Kowluru A: Novel Regulatory Roles of Small G Protein Guanine Dissociation Stimulator (smgGDS) in Insulin Secretion from Pancreatic β-Cells. Molecular and Cellular Endocrinology 580:112104. doi: 10.1016/j.mce.2023.112104, 2024

Hali M, Pinto N, Kowluru A: Regulatory roles of histone deacetylation in metabolic stress-induced expression of caspase recruitment domain family member 9 (CARD9) in pancreatic β-cells. Int J Mol Sci. 24(21):15994. doi: 10.3390/ijms242115994, 2023. [PMID: 37958977]

Gleason N, Kowluru A: Hyperglycemic stress induces expression, degradation, and nuclear association of Rho GDP-dissociation inhibitor 2 in pancreatic beta cells. Cells 13, 272.https://doi.org/10.3390/cells13030272, 2024.

Kowluru RA, Kowluru A: Epigenetics of diabetes in humans. In Epigenetics in Human Disease. Trygve Tollefsbol (ed) Elsevier. Volume 1:491-515, 2024.

ACTIVE RESEARCH SUPPORT

I01 BX004663-01 [Merit Award, Department of VA]
Duration: 01/01/2020-12/31/2024 
Islet Beta Cell Dysfunction Under Metabolic Stress [continuous support of MERIT REVIEW award for years 27-31]

K6 BX005383 [Department of VA-Senior Research Career Scientist Award
Duration: 10/01/2020-09/30/2027 
Senior Research Career Scientist Award [Continuous support from the VA for years 20-26].
Role: PI

5RO 1EY022230-04 [NIH/NEI]
Duration: 04/01/2012-03/31/2024
NADPH Oxidase, Mitochondrial Dysfunction and Diabetic Retinopathy
Role: PI [Multi-PI award with Dr. Renu Kowluru]. Competing renewal under revision.

I01BX006377-01A1 [Merit Award, Department of VA]
Duration: 01/01/2025-12/31/2028 (continuous support of MERIT REVIEW for years 32-36)
Aberrant nuclear signaling in the islet beta cell under metabolic stress 
Role: PI

Courses taught by Anjaneyulu Kowluru, MSc, Ph.D.

Fall Term 2024 (current)

Fall Term 2023

Fall Term 2022

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