Complement: Its nuances in health and disease: The focus of my lab is to study the role of complement in the kidney and brain. There is a resurgence of interest in the complement field due to a growing list of novel and non-canonical complement functions, increase in functional locations and rapidly expanding list of complement therapeutics. Complement activation is a crucial event for maintaining health. However, if it is overwhelmed or restricted, it can be destructive, causing disease pathology. Recently, it has been recognized and appreciated that complement is synthesized at different locale and the intrinsic complement modulates microenvironmental homeostasis. The goal of the kidney arm of the work is to understand glomerular inflammation using the immune complex mediated glomerulonephritis mouse model. Complement signaling directs macrophages (MØs) to sites of inflammation, the numbers of which correlate negatively with organ function. We are studying the mechanisms at play in the regulation of trafficking and polarization of MØs by complement. The kidney is the size of a human fist (0.5% body weight). Yet 20-25 % of cardiac output traverses the kidney with filtration of toxic wastes occurring at the glomeruli, rendering it vulnerable to injury, resulting in loss of renal function. Endothelial layer is an integral part of the kidney filtration unit. Our recent studies revealed for the first time that intrinsic endothelial complement is of significance in maintaining kidney endothelial layer integrity. The molecular pathways involved is the focus of ongoing studies. Our studies showed that inhibition of complement protected the blood-brain barrier (BBB) integrity, reduced the severity of disease and improved brain function in systemic lupus erythematosus (lupus) model. The goal of the brain arm of the work is to understand CNS inflammation using the lupus mouse model, specifically the role of complement in it. The BBB consists of endothelial cells, astrocytic end feet and pericytes, and protects the brain from systemic circulation. Complement activation generates small molecules such as C5a, that bind to its G-coupled receptor and alters the structural integrity of the BBB. We are currently studying the complement dependent pathways involved in brain endothelial cells. These studies will open avenues for identification of novel therapeutics for diseases that have no effective therapies and will contribute to shaping the expanding complement therapeutic toolbox.
Education and Training:
PhD, Biochemistry, University of Hyderabad (1990)
MS, Science with Zoology, Osmania University (1982)
Associate Editor, Frontiers in Immunology (2022-present)
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)
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) Production and Functional Analysis of Rat CD59 and Chimeric CD59-Crry as Active Soluble Proteins in Pichia Pastoris. Immunology (Jan)99-46.
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. (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.
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
International Society of Neurochemistry (2014–present)
American Association of Immunologists (2010–present)
American Society of Clinical Investigation (2009–present)
Complement Society (2005–present)
"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)