Complement: Its nuances in health and disease: The lab has 2 ongoing projects: The first one is to study the role of the complement (C) system in the kidney and brain in normal and disease settings. C discovered by Jules Bordet in the 1800s is one of the critical mechanisms involved in human defense. The exciting work in the last decade has revealed that in addition to the established function of host defense, C also participates in several novel non-canonical functions, and has functional specificities at different locations, that have led to a rapidly expanding C therapeutics arena. C regulators strictly modulate the C system, preventing injury to host tissue. The absence of C factor H (FH), a critical regulator of the alternative C pathway causes loss of kidney function in men and mice. The goal of the kidney arm of the work is to understand the role of FH in glomerular inflammation, using the immune complex-mediated glomerulonephritis (ICGN) mouse model. Bone marrow and kidney transplant studies in the lab revealed that ICs were transported by FH on platelets in mice and processed by FH on kidney podocytes. In addition, our results showed that circulating FH played a critical role in causing kidney disease pathology. Since significant macrophage (MØs) infiltration occurred in the kidneys in this disease setting, and depletion of MØs in mice alleviated the pathology we are determining the role of these cells and the underlying mechanisms involved. We are studying the role of extrinsic and intrinsic C on MØs in this setting and the mechanisms at play in the regulation of trafficking and polarization of MØs by FH. Another observation in this disease setting is the subendothelial deposits. The endothelial layer is an integral part of the kidney filtration unit. Using cultured endothelial cells isolated from wildtype and FH knockout mice, our recent studies revealed for the first time that intrinsic endothelial C is of significance in maintaining kidney endothelial layer integrity. The translatability of the results was established using human endothelial cells transfected with FH SiRNA. The molecular pathways involved are the focus of ongoing studies. One of the commonalities between the brain and the kidney is that both organs filter the blood passing through. We study the role of C in the brain focusing on the systemic lupus erythematosus (lupus) model and 2D cell culture systems. Our results show that C inhibition protected the blood-brain barrier (BBB) integrity, reduced the severity of the disease, and improved behavior in lupus. C5a generated during C activation alters the structural integrity of the BBB by signaling through the G-coupled receptor, C3aR. We are currently studying the C-dependent pathways involved in brain endothelial cells. The second project that is currently ongoing is to study the role of the microbiome and the C connection in different inflammatory diseases such as lupus in men and mice. The collection of samples to determine how the microbiome impacts the disease in lupus patients in India was initiated through a Fulbright scholarship. We are grateful for the support of the Community of Excellence for Global Health Equity and the Office of the Vice President of Research, UB that has allowed us to begin processing and analysis of these samples. With the support of Genome, Environment, and Microbiome (GEM, UB), we have accrued the microbiome samples from mice, and the sequencing and analysis are currently ongoing.
Education and Training:
Certificate, AI Generalist Certification, Outskill (2025)
Other, AI Tools 101 for Transforming Online Learning, Inside Higher Ed: Honorlock (2025)
PhD, Biochemistry, University of Hyderabad (1990)
MS, Science with Zoology, Osmania University (1982)
Employment:
Associate Director, MD/PhD program, Jacobs School of Medicine and Biomedical Sciences (2025-present)
Associate Director, MD/PhD program, MD/PhD, University at Buffalo (2025-present)
Councilor, International Complement Society (2025-present)
Associate Editor, Immunobiology (2024-present)
Section editor, Immunobiology (2024-present)
Adjunct Faculty, Physiology and Biophysics, JSMBS, University at Buffalo (2023-present)
Topic Editor, Women in MS and Neurodegeneration, Frontiers in Neurology (2023-present)
Associate Editor, Bcell biology, Frontiers in Immunology (2022-present)
Topic Editor, Complement & Autoimmunity, Frontiers in Immunology (2022-present)
Adjunct Faculty, Eerie Community College (2017-present)
Adjunct Faculty, Trocaire (2016-present)
Member, Neuroscience Program, University at Buffalo (2016-present)
Graduate Faculty, Medicine, University at Buffalo (2017-present)
Member, Neuroscience Program, University at Buffalo School of Health Related Professions (2016-present)
Research Professor, School of Medicine and Biomedical Sciences, University at Buffalo (2015-present)
Diversity Advocate, Department of Medicine, University at Buffalo (2021–2023)
Diversity Advocate, Medicine, University at Buffalo (2020–2023)
Faculty Senate Secretary, University at Buffalo (2017–2022)
American Association of Immunology Lab grant (2024)
panelist (2022)
2021 Lab grant, American Association of Immunology (2021)
Individual Development Award (2021)
Excellence in Immunology (2019)
Faculty Award of Excellence for promoting inclusion and cultural diversity (2019)
Fulbright Scholar (2019)
Manuscript published received editorial invite since it got 2537 downloads in a year (2018)
SUNY award ‘Conversations in the Disciplines’ (2017)
Article chosen for cover page by Immunology journal (2015)
Article chosen for cover page by Immunology journal (2014)
Invited speaker (2007)
Journal of Immunology paper given write up in Lupus Research Update (2006)
Invited speaker at the MPGN Type II Focus Group: Towards a Cure, UK (2006)
Paper in Inaugural Issue of Fast Track Manuscripts, JASN (2004)
Abstract chosen by the American Society of Nephrology (2004)
Certificate for Original Research, Neuroscience Program Committee, Chicago Medical School (1992)
ICMR travel award (1990)
American Society of Neurochemistry Travel Award (1989)
Chosen as “highlights from literature”: Hyperammonemia causes many changes found after portacaval shunting, Biochem. J., 272:311-317, by Cerebrovascular and Brain Metabolism Reviews (1989)
SS Parmer Foundation Award (1986)
Senior Research Fellowship, CSIR, India (1984)
Junior Research Fellowship, CSIR, India (1982)
National Merit Scholarship (1975)
Research Expertise:
Experimental renal inflammation
Monocytes in circulation and Macrophages in tissues
Mouse models of sterile inflammation and autoimmunity
Neuropsychiatric lupus
Nuances of complement and endothelial cells
Pathobiology of the complement system
Research Centers:
Clinical and Translational Research Center (CTRC)
UB 2020 Strategic Strengths:
Molecular Recognition in Biological Systems and Bioinformatics
Grants and Sponsored Research:
July 2018–July 2021 Mechanisms of Complement Dependent Immune Complex-Mediated Glomerulonephritis National Institute of Health Role: Principal Investigator $717,750
January 2018–December 2018 American Hearing Research Foundation American Hearing Research Foundation Role: Principal Investigator $20,000
January 2018–April 2018 course infusion award University at Buffalo Role: Principal Investigator $785
February 2007–February 2012 “Role of the Complement System in Renal Disease.” NIH Role: Co-Investigator
October 2002–December 2011 Kidneed Foundation Kidneed Foundation Role: Principal Investigator $250,000
February 1998–February 2006 “Role of the Complement System in Glomerulonephritis,” NIH Role: Co-Investigator
February 1999–February 2003 “Pathogenic Role of the Complement System in Murine Lupus” NIH Role: Co-Investigator
January 1999–January 2001 Arthritis Foundation Arthritis Foundation Role: Principal Investigator $90,000
March 1992–March 1994 Omega oxidation and Reyes syndrome. NIH Role: Principal Investigator $50,000
Alexander Jacob, Michael Phelps, Shane Fraher, Marcos Lopez, Anthony Chang, Richard J. Quigg, and Jessy J. Alexander. (2022) Macrophage depletion reduces disease pathology in factor H dependent immune complex-mediated glomerulonephritis. Journal of Immunology Research (Jan)
Jacob A, Nina Peralta L, Pegues D, Okamura K, Chang A, McSkimming D, Alexander J. (2021) Exercise alleviates symptoms of CNS lupus. Brain Research (Jul)(1765): 147478. doi:0.1016/j.brainres
Alexander JJ, Jacob A, Quigg RJ. (2015) Effects of Conventional Immunosuppressive Therapy on Functional and Pathological Features of CNS Lupus in NZB/W Mice. F1000Research (Jun), 4: 163-173.
Eadon MT, Hack BK, Alexander JJ, Xu C, Dolan ME, Cunningham PN. (2013) Cell Cycle Arrest in a Model of Colistin Nephrotoxicity. Physiol Genomics (Jul), Epub.
Alexander JJ. (2007) New Approaches to the Treatment of Dense Deposit Disease. J Am Soc Nephrol. (Jan), 18: 2447-2456.
Alexander JJ. (2007) Systemic lupus erythematosus and the brain: What mice are telling us. Neurochem Int. (Jan), 50: 5.
Alexander JJ. (2007) Rodent Factor H Functions as a Counterpart of Human CR1 in Renal Immune Complex Processing. J Am Soc Nephrol (Jan), 18: 1157-1166.
Alexander JJ. (2003) Rat Glomerular Epithelial Cells Produce and Bear Factor H on their Surface that is Up-regulated Under Complement Attack. Kidney Int (Jan), 64: 914.
Alexander JJ. (2003) Administration of the Soluble Complement Inhibitor, Crry-Ig, Reduces Inflammation and Aquaporin 4 Expression in Lupus Cerebritis. Biochim Biophys Acta. (Jan), 1639: 169-176.
Alexander JJ. (2002) Prominent Renal Expression of a Murine Leukemia Retrovirus in Experimental Systemic Lupus Erythematosus. J Am Soc Nephrol. (Jan), 13: 2869.
Alexander JJ. (2002) Injury in Renal Ischemia-reperfusion is Independent from Immunoglobulins and T Lymphocytes. Am J Physiol Renal Physiol (Jan), 282: F352-F357.
Alexander JJ. (2002) A Complement-dependent Model of Thrombotic Thrombocytopenic Purpura Induced by Antibodies Reactive with Endothelial Cells. Clinical Immunology (Jan), 103: 43-53.
Alexander JJ. (2002) Genetic Inhibition of the Complement Cascade Accelerates Alzheimer’s Pathology in Transgenic Mice. PNAS (Jan), 99: 10837-10842.
Alexander JJ. (2001) Factor H is Present on Rodent Platelets and Functions as the Immune Adherence Receptor. JBC (Jan), 276: 32129-32135.
Alexander JJ. (2000) Complement is Activated in Kidney by Endotoxin but does not Cause the Ensuing Acute Renal Failure. Kidney Int. (Jan), 58: 1580.
Alexander JJ. (2000) Production and Functional Analysis of Rat CD59 and Chimeric CD59-Crry as Active Soluble Proteins in Pichia Pastoris. Immunology (Jan)99-46.
Alexander JJ. (1999) Renal, Central Nervous System and Pancreatic Overexpression of Recombinant Soluble Crry in Transgenic Mice. A Novel Means of Protection from Complement-mediated Injury. Immunopharmacology (Jan), 42: 245-254.
Alexander JJ. (1998) Immune Complex Glomerulonephritis in C4- and C3-Deficient Mice. Kidney Int. (Jan), 53: 32.
Alexander JJ. (1998) Inhibition of Complement Regulation is Key to the Pathogenesis of Active Heymann Nephritis. J Exp. Med. (Jan), 188: 1353.
Alexander JJ. (1997) Production of the Rat Complement Regulator, Crry, as an Active Soluble Protein in Pichia Pastoris. Arch. Biochem. Biophys (Jan), 341: 3.
Alexander JJ. (1997) Characterization of C3 Receptors on Cultured Rat Glomerular Endothelial Cells. Kidney International (Jan), 51: 1124.
Alexander JJ. (1997) Characterization of C3-binding Proteins on Mouse Neutrophils and Platelets. J Immunol. (Jan), 159: 2438.
Alexander JJ. (1995) Molecular Characterization of Rat Crry: Widespread Distribution of Two Alternative Forms of Crry mRNA. Immunogenetics (Jan), 42: 362.
Alexander JJ. (1993) Alterations in Mitochondrial Branched-chain Amino Acid Metabolism in Brain in Acute Hyperammonemic States. Neuroscience Letters (Jan), 149: 221-224.
Chang A., P. Kadambi and J. J. Alexander. (2006) Encyclopedic Reference of Molecular Mechanisms of Disease. In: Membranoproliferative Glomerulonephritis. Springer Verlag
Alexander JJ and Hawkins R. (1994) In Hepatic Encephalopathy, Hyperammonemia and Ammonia toxicity. In: Neomycin Reduces the Metabolic Ability of the Small Intestine to Produce Ammonia from Glutamine. Plenum Press
Alexander JJ. (1989) .Hepatic Encephalopathy. In: Acute Action of Ammonia on Leucine Metabolism in Isolated Astrocytes, Neurons and Oligocells of Rat Brain. Humana Press
Alexander JJ. (1989) In: Cellular and Subcellular Branched-chain Keto Acid Decarboxylase in Rat Brain and its Response to Hyperammonemia.
Alexander JJ and Murthy RK. (1987) Biochemical Pathology of Astrocytes. In: Cerebral Cellular Branched-chain Amino Acid Transaminases in Hyperammonemia. Alan R.Liss.
Alexander JJ and Murthy RK. (1987) In Biochemical Pathology of Astrocytes. In: Acute Effects of Ammonia on the Metabolism of Isolated and Cultured Astrocytes. Alan R. Liss
Abstracts:
Supriya D. Mahajan, Jessy Alexander. (2025) Role of Complement Activation in HIV Neuropathogenesis Associated with Methamphetamine (METH) Abuse. 2025 NIDA Genetics and Epigenetics Cross-Cutting Research Team Meeting, (Mar)
Professional Memberships:
International Society of Neurochemistry (2014–present)
American Association of Immunologists (2010–present)
American Society of Clinical Investigation (2009–present)
Complement Society (2005–present)
Presentations:
"Macrophage-Derived Complement Factor H Restrains Kidney Inflammation and Fibrosis in Immune Complex-Mediated Disease" International complement workshop (2025)
"“Location matters: the evolving roles of cell-autonomous and local complement”." Co-organizer; ICS Guest Symposium, Annual meeting of the American Association of Immunology. Washington DC (2023)
"“Complement: An Old Field with new Insights”" Grand Rounds (2022)
"Bio-STEM Scientific Discovery Series" Bio-STEM Scientific Discovery Series as part of the CLIMB UP/iSEED Summer Research Program (2022)
"Effective undergraduate research mentoring panel" CSTEP (2022)
"Intracellular complement and kidney disease." International complement society symposium: Complement: The road less traveled at the American Association of Immunology (2022)
"Complement and its non-canonical functions" Christian Medical College, Vellore, India (2022)
"Role of Factor H in macrophages" Toronto Complement Conference (2021)
"“Complement factor H: A story unfolding”." Seminar, Kidney diseases branch, NIH (2021)
"Complement Factor H regulates kidney function by modulating macrophages" American Association of Immunology-Virtual conference. (2021)
"Effective Undergraduate Research Panel" CSTEP program (2021)
"“Complement and the kidney.”" Department of Immunology & Microbiology, University of Pittsburg, PA. (2020)
"Complement and the kidney" Seminar, Wayne State University (2020)
"“Complement and blood-brain barrier integrity.”" International Society of Neurochemistry/American Society of Neurochemistry (2019)
"“Complement in health and disease”" Fulbright lecture series, GITAM University (2019)
"“Understanding the role of complement in CNS lupus towards personalized medicine and drug development”" 5th Meeting on Precision Medicine (2019)
"A journey with complement & kidney" Women in Science, CTRC, UB (2019)
"“Complement in health and disease”" University at Buffalo Dental School (2019)
"1. Complement in the brain during health and disease 2. Complement and blood-brain barrier in lupus 3. Complement in kidney during health and disease 4. Double negative T cells and lupus" Lecture series, Rheumatology, Christian Medical College, Vellore, India (2019)
"C5a/C5aR1 signaling alters blood-brain barrier integrity and brain function in systemic lupus erythematosus" European complement-based Drug development summit (2018)
"“Cultural competence in healthcare”" UB’s First: Living Our Commitment: UB’s Inaugural Summit on Inclusive Excellence” (2018)
"Lupus and Complement" Section of Nephrology, University at Buffalo (2018)
"“Complement as a modulator of Neurodegeneration in lupus.”" Dept. of Cell & Molecular Biology, SUNY Downstate Medical Center, (2017)
"Macrophages and complement-the culprits in glomerulonephritis" "Fueling conversations in Complement", Buffalo, NY (2017)
"Specific Targeting of Complement Pathways for Clinical Benefit" American Association of Immunology; American Association of Immunology; Complement (2016)
"Complement and the blood-brain barrier" Interdisciplinary Conversations in Blood-Brain Barrier Re-modelling (2016)
"Unexpected Roles for Immune Signaling in the Healthy and Diseased Brain" American Society of Neurochemistry (2013)
"Role of Factor H in kidney disease" Section of Nephrology, University of Chicago (2012)
"Complement in Hepatic Encephalopathy" I.S.H.E.N. 14th symposium on Hepatic Encephalopathy & Nitrogen metabolism. (2010)
"Distinct and separable role of FH in chimaeric mice" Dense Deposit Disease; Kidneeds/Wellcome Group (2008)
"The Complement Cascade: Yin-Yang in Neuroinflammation: Neuro-protection and degeneration" American Society of Neurochemistry (2008)
"Complement factor H on podocytes serve as immune adherence receptor similar to CR1 in humans" DDD Focus Group, Welcome Trust, UK (2007)
"Distinct and separable roles of the complement system in factor H- deficient bone marrow chimeric mice with immune complex disease" MPGN Focus Group, Welcome Trust, UK (2005)
"Complement: Good and Bad" American Society of Neurochemistry (2004)
"Complement in the brain: New and exciting insights in an old arena of Immunology" American Society of Neurochemistry (2003)
Precision Clinical Medicine, Oxford Academic; Editorial Board member (2022)
Discovery Immunology, Official Journal of British Society of Immunology; Member of Editorial Board (2022–2026)
Natural Sciences Interdisciplinary Master's program; Steering committee member (2021–present)
Social justice team, St Pauls Cathedral; Member (2021–present)
Pastoral care team, St Pauls cathedral; Member (2021–present)
Frontiers in Immunology; Review Editor (2021–present)
Vestry, St. Paul's Cathedral, Downtown Buffalo; Member (2021–2023)
PPBS; Admissions committee member (2021–present)
Innate Immunity and Inflammation; Standing study section Member (2019–2023)
Celebration of Scholarship; Judge (2019–present)
BDCN-E (04): Neurobiology of Brain Degenerative Disorders, Autoimmune Disea;; Ad Hoc Reviewer (2019)
Presenter: Bio-STEM Scientific Discovery Series for CLIMB and iSEED undergraduates on career development and research (2019)
American Association of University Women; 2019-21 Research Publication Grant;; Grant Reviewer (2019–present)
NIH; Hypersensitivity, Autoimmunity & Immunity Study Section III;; Ad Hoc Reviewer (2019–present)
NIH; Innate Immunity Study Section III;; Ad Hoc Reviewer (2019–present)
Faculty senate Bylaws committee; Member (2018–2025)
BDCN-E (04): Neurobiology of Brain Degenerative Disorders, Autoimmune Disea;; Ad Hoc Reviewer (2018–present)
Presenter: Workshop for CLIMB PhD scholars regarding the importance of Cultural Competency as part of the Professional Development Catalyst (PDC) workshop series (2018)
American Association of University Women;; Grant Reviewer (2018–2019)
Search committee for Center for Diversity Innovation Director; Member (2018)
NIH; Special Emphasis Panel ZRG1 VH-N 80 A, Vascular and Hematology;; Ad Hoc Reviewer (2018–present)
Wellcome Research Foundation, UK;; Ad Hoc Reviewer (2018–present)
University of Sharjah, UAE;; Ad Hoc Reviewer (2018–present)
German Research Foundation;; Ad Hoc Reviewer (2018–present)
NIH; Anonymization Study by CSR;; Grant Reviewer (2018–present)
Steering Committee to Study Promotion and Professional Development of Faculty in Qualified Ranks; Member (2018–present)
UB Faculty Senate Secetary (2017–2022)
Presenter: Workshop for students regarding the importance of Cultural Competency iSEED students (2017–2018)
Subcommittee Inclusion & Engagement of International Students Task Force : “Recruitment and Communications Strategy”; Member (2017–2018)
CSTEP Summer Research Program; Research Symposium Judge (2017–present)
CLIMB UP Mentor; CLIMB UP Mentor (2016–2025)
Faculty senate executive committee; Member (2016–2023)
CSTEP program Mentor; CSTEP program Mentor (2016–2025)
Medicine Research Day; Judge (2016–2018)
Grant reviewer: CTSI; Grant reviewer: CTSI (2016–2017)
Israel Science Foundation;; Ad Hoc Reviewer (2016–present)
MRC England;; Ad Hoc Reviewer (2015–2024)
Ad hoc panel for promotions in Research track; Univ. at Buffalo; Member (2014–2023)
CLIMB-PRO Mentoring of undergraduates during summer; Mentor (2014)
NIH; Innate Immunity III;; Ad Hoc Reviewer (2014–2016)
Pennsylvania Department of Health and the Oak Ridge Associated Universities;; Ad Hoc Reviewer (2013–present)
Frontiers in Immunology, J. Neuroinflammation, J. Neurochemistry, Molecular Immunology, Brain Research, etc,; Adhoc Manuscript Reviewer (2010–present)
Institutional Animal Care and Use Committee, University of Chicago; Member (2009–2013)