J. Andres Melendez
Post Doctoral Fellow, Department of Biochemistry, Albany Medical College, 1997
- Post Doctoral Associate, Division of Lung Biology, Georgetown University Medical Center, 1995
- Ph.D., Biological Sciences, with a concentration in Molecular Biology, University at Albany, State University of New York, 1992
Past Professional Experience
- Associate Professor, Center for Immunology & Microbial Disease, Albany Medical College, 2011
- Assistant Professor, Center for Immunology & Microbial Disease, Albany Medical College, 2005
- Research Assistant Professor, Department of Biochemistry, Albany Medical College, 2001
Areas of Research
- Free Radical Biology
- Cellular and organismal aging biology
- Matrix Remodeling
- Host & Pathogen interactions
Our studies revolve around a key central paradigm, that oxidant signaling is precise, compartmentalized and amenable to targeted‐antioxidant based therapies. Reactive oxygen and nitrogen species (ROS/RNS), in addition to their ability to damage biomolecules, have also emerged as key mediators in regulation of signaling networks by modulating phosphatase activity, kinase cascades and transcription factor binding. Thus, ROS/RNS serve a dual role, at low concentrations they are secondary signaling molecules that regulate the expression of a wide array of signaling networks, and at high concentrations damage lipids, protein and DNA. The principle mediator of ROS‐dependent signaling is the 2e‐ reduction product of oxygen, H2O2, which is produced in response to numerous physiologic stimuli. Recent work from my lab and others indicate that superoxide (O2‐•) may also play an important role in cellular signal regulation.
Our work is focused on defining how ROS/RNS drive cellular signaling events that control metastatic disease, matrix destruction and the virulence of infectious bacteria. We have developed many cutting edge tools to monitor oxidant production from cells in real time. These assays are still fairly labor intensive and require a great deal of both biochemical and molecular expertise. CNSE technologies are being applied to develop nano-devices to assess cellular redox state. We are also performing high throughput screening (HTS) for agents that restrict age associated matrix destruction. Lastly our group is developing targeted‐antioxidant based therapeutics to be released at sites of matrix degradation. Our studies indicate that aberrant proteolysis is commonly linked to augmented free radical production that initiate or drive disease associated matrix destruction. Development of antioxidants that are released upon proteolysis at the precise site of oxidant production would then in turn ameliorate matrix destruction. CNSE is unique and provides the scientific infrastructure for the development of innovative therapeutic and diagnostic technologies to meet the medical demands of our aging population.
Honors and Awards
Sigma Xi support in aid of research
National Hispanic Scholarship
ASCB Minority Travel Fellowship
National Cancer Institute Minority Predoctoral Fellowship
NIDDK Minority Travel Fellowship
NHLBI Minority Postdoctoral Fellowship
Abstract Award Speaker Gordon Conference “Antioxidant Nutrients in the Cellular Biology of Health and Disease” Aug 12-17,1995.
NICHD Minority Postdoctoral Fellowship
Oxygen Society Outstanding Scientific Research Presentation
AACR Minority Scholar Travel Award
Sosa Academy of Medicine Outstanding Mentor Award
Standing Member, NIH NCI Cancer Etiology Study Section
Free Radiacal Biology and Medicine
Shakerley NL, Chandrasekaran A, Trebak M, Miller BA, Melendez JA. Francisella
tularensis Catalase Restricts Immune Function by Impairing TRPM2 Channel
Activity. J Biol Chem. 2016 Feb 19;291(8):3871-81.
Rabadi SM, Sanchez BC, Varanat M, Ma Z, Catlett SV, Melendez JA, Malik M,
Bakshi CS. Antioxidant defenses of Francisella tularensis modulate macrophage
function and production of proinflammatory cytokines. J Biol Chem. 2015 Dec 7.
Flaherty NL, Chandrasekaran A, del Pilar Sosa Peña M, Roth GA, Brenner SA,
Begley TJ, Melendez JA. Comparative analysis of redox and inflammatory properties
of pristine nanomaterials and commonly used semiconductor manufacturing
nano-abrasives. Toxicol Lett. 2015 Dec 15;239(3):205-15.
Shin DH, Dier U, Melendez JA, Hempel N. Regulation of MMP-1 expression in
response to hypoxia is dependent on the intracellular redox status of metastatic
bladder cancer cells. Biochim Biophys Acta. 2015 Dec;1852(12):2593-602.
Endres L, Begley U, Clark R, Gu C, Dziergowska A, Małkiewicz A, Melendez JA,
Dedon PC, Begley TJ. Alkbh8 Regulates Selenocysteine-Protein Expression to
Protect against Reactive Oxygen Species Damage. PLoS One. 2015 Jul6;10(7):e0131335.
Bartling TR, Subbaram S, Clark RR, Chandrasekaran A, Kar S, Melendez JA.
Redox-sensitive gene-regulatory events controlling aberrant matrix
metalloproteinase-1 expression. Free Radic Biol Med. 2014 Sep;74:99-107
Hynes WF, Doty NJ, Zarembinski TI, Schwartz MP, Toepke MW, Murphy WL, Atzet
SK, Clark R, Melendez JA, Cady NC. Micropatterning of 3D Microenvironments for
Living Biosensor Applications. Biosensors (Basel). 2014 Mar;4(1):28-44.
Hempel N, Melendez JA. Intracellular redox status controls membrane
localization of pro- and anti-migratory signaling molecules. Redox Biol. 2014 Jan20;2:245-5
Hempel N, Bartling TR, Mian B and J. A. Melendez. Acquisition of the Metastatic Phenotype Is Accompanied by H2O2-Dependent Activation of the p130Cas Signaling Complex. Mol Cancer Res. 2013 Mar;11(3):303-12.
McCarthy, DA, Ranganathan, A, Subbaram, S, Flahety, NL, Patel, N, Trebak, M, Hempel, N and J. A. Melendez. Redox-control of the alarmin, Interleukin-1α. Redox Biology, 2013 Apr 17;1(1):218-25. doi: 10.1016/j.redox.2013.03.001.
Franchini A, Hunt D, Melendez, J. A. and Drake J*. FcγR Driven Release of IL-6 by Macrophages Requires NOX2-Dependent Production of Reactive Oxygen Species. J. Biol Chem, 2013 Aug 30;288(35):25098-108.
McCarthy DA, Clark RR, Bartling TR, Trebak M, Melendez JA. Redox-control of the senescence regulator Interleukin-1 α and the secretory phenotype. J Biol Chem. 2013 Sep 23.
Hempel N, Carrico PM, Melendez JA. Manganese superoxide dismutase (Sod2) and redox-control of signaling events that drive metastasis. Anticancer Agents Med Chem. 2011 Feb;11(2):191-201. PubMed PMID: 21434856.
Kar S, Subbaram S, Carrico PM, Melendez JA. Redox-control of matrix metalloproteinase-1: a critical link between free radicals, matrix remodeling and degenerative disease. Respir Physiol Neurobiol. 2010 Dec 31;174(3):299-306. Epub 2010 Sep 8. Review. PubMed PMID: 20804863; PubMed Central PMCID: PMC2991541.
Dasgupta J, Kar S, Liu R, Joseph J, Kalyanaraman B, Remington SJ, Chen C,Melendez JA. Reactive oxygen species control senescence-associated matrixmetalloproteinase-1 through c-Jun-N-terminal kinase. J Cell Physiol. 2010 Oct;225(1):52-62. PubMed PMID: 20648623; PubMed Central PMCID: PMC2913426.
Melillo AA, Bakshi CS, Melendez JA. Francisella tularensis antioxidants harness reactive oxygen species to restrict macrophage signaling and cytokine production. J Biol Chem. 2010 Sep 3;285(36):27553-60. Epub 2010 Jun 17. PubMedPMID: 20558723; PubMed Central PMCID: PMC2934622.
Melillo AA, Mahawar M, Sellati TJ, Malik M, Metzger DW, Melendez JA, BakshiCS. Identification of Francisella tularensis live vaccine strain CuZn superoxide dismutase as critical for resistance to extracellularly generated reactive oxygen species. J Bacteriol. 2009 Oct;191(20):6447-56. Epub 2009 Aug 14. PubMed PMID:19684141; PubMed Central PMCID: PMC2753026.
Epperly MW, Melendez JA, Zhang X, Nie S, Pearce L, Peterson J, Franicola D,Dixon T, Greenberger BA, Komanduri P, Wang H, Greenberger JS. Mitochondrialtargeting of a catalase transgene product by plasmid liposomes increases radioresistance in vitro and in vivo. Radiat Res. 2009 May;171(5):588-95. PubMed PMID: 19580494; PubMed Central PMCID: PMC2762783.
Dasgupta J, Kar S, Van Remmen H, Melendez JA. Age-dependent increases in interstitial collagenase and MAP Kinase levels are exacerbated by superoxide dismutase deficiencies. Exp Gerontol. 2009 Aug;44(8):503-10. Epub 2009 May 3. PubMed PMID: 19409972; PubMed Central PMCID: PMC2827242.
Subbaram S, Melendez JA, Chittur SV. Method for conducting microarray study of oxidative stress induced gene expression. Methods Mol Biol. 2008;477:357-68.PubMed PMID: 19082960.
Hempel N, Ye H, Abessi B, Mian B, Melendez JA. Altered redox status accompanies progression to metastatic human bladder cancer. Free Radic Biol Med. 2009 Jan 1;46(1):42-50. Epub 2008 Oct 1. PubMed PMID: 18930813; PubMed Central PMCID: PMC2630461.
Bakshi CS, Malik M, Mahawar M, Kirimanjeswara GS, Hazlett KR, Palmer LE,Furie MB, Singh R, Melendez JA, Sellati TJ, Metzger DW. An improved vaccine for prevention of respiratory tularemia caused by Francisella tularensis SchuS4 strain. Vaccine. 2008 Sep 26;26(41):5276-88. Epub 2008 Aug 8. PubMed PMID: 18692537; PubMed Central PMCID: PMC2652725.
Connor KM, Hempel N, Nelson KK, Dabiri G, Gamarra A, Belarmino J, Van De Water L, Mian BM, Melendez JA. Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells. Cancer Res. 2007 Nov 1;67(21):10260-7. PubMed PMID: 17974967.
Malik M, Bakshi CS, McCabe K, Catlett SV, Shah A, Singh R, Jackson PL, GaggarA, Metzger DW, Melendez JA, Blalock JE, Sellati TJ. Matrix metalloproteinase 9 activity enhances host susceptibility to pulmonary infection with type A and B strains of Francisella tularensis. J Immunol. 2007 Jan 15;178(2):1013-20. PubMed PMID: 17202364.
Pardo M, Melendez JA, Tirosh O. Manganese superoxide dismutase inactivation during Fas (CD95)-mediated apoptosis in Jurkat T cells. Free Radic Biol Med. 2006 Dec 15;41(12):1795-806. Epub 2006 Sep 16. PubMed PMID: 17157182.
Ding J, Zhang X, Li J, Song L, Ouyang W, Zhang D, Xue C, Costa M, Meléndez JA, Huang C. Nickel compounds render anti-apoptotic effect to human bronchial epithelial Beas-2B cells by induction of cyclooxygenase-2 through an IKKbeta/p65-dependent and IKKalpha- and p50-independent pathway. J Biol Chem. 2006 Dec 22;281(51):39022-32. Epub 2006 Sep 18. PubMed PMID: 16982623.
Bakshi CS, Malik M, Regan K, Melendez JA, Metzger DW, Pavlov VM, Sellati TJ. Superoxide dismutase B gene (sodB)-deficient mutants of Francisella tularensis demonstrate hypersensitivity to oxidative stress and attenuated virulence. J Bacteriol. 2006 Sep;188(17):6443-8. PubMed PMID: 16923916; PubMed Central PMCID: PMC1595384.
Dasgupta J, Subbaram S, Connor KM, Rodriguez AM, Tirosh O, Beckman JS, Jourd'Heuil D, Melendez JA. Manganese superoxide dismutase protects from TNF-alpha-induced apoptosis by increasing the steady-state production of H2O2. Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1295-305. PubMed PMID: 16910777.
Pimentel DR, Adachi T, Ido Y, Heibeck T, Jiang B, Lee Y, Melendez JA, Cohen RA, Colucci WS. Strain-stimulated hypertrophy in cardiac myocytes is mediated by reactive oxygen species-dependent Ras S-glutathiolation. J Mol Cell Cardiol. 2006Oct;41(4):613-22. Epub 2006 Jun 27. PubMed PMID: 16806262.
Nelson KK, Subbaram S, Connor KM, Dasgupta J, Ha XF, Meng TC, Tonks NK, Melendez JA. Redox-dependent matrix metalloproteinase-1 expression is regulated by JNK through Ets and AP-1 promoter motifs. J Biol Chem. 2006 May 19;281(20):14100-10. Epub 2006 Mar 28. PubMed PMID: 16569638.
Arita Y, Harkness SH, Kazzaz JA, Koo HC, Joseph A, Melendez JA, Davis JM, Chander A, Li Y. Mitochondrial localization of catalase provides optimal protection from H2O2-induced cell death in lung epithelial cells. Am J PhysiolLung Cell Mol Physiol. 2006 May;290(5):L978-86. Epub 2005 Dec 30. PubMed PMID:16387755.
Invited Lectures and Presentations
Oxygen Society Workshop Lecture: “ Molecular Biological Approaches to Free Radical Research”
Oxygen Society Plenary Lecture: “Mitochondrial Hydrogen Peroxide in tumorigenesis: Friend or Foe.”
Gordon Research Conference Plenary Lecture: “Mitochondrial Hydrogen Peroxide & Signal Transduction”.
Warburg Conference on Tumor Metabolism
Oxygen Society Plenary Lecture: “Mitochondrial redox-control of matrix degradation”
16th Annual Society for Free Radical Biology and Medicine Plenary Session Chair
Society for Basic Urologic Research, Fall Symposium, Plenary Lecture “Redox-Control of Bladder Cancer Invasion and Metastasis” November 11-14, 2010. Atlanta, GA.
17th Annual Society for Free Radical Biology and Medicine Session Chair “Superoxide and Superoxide dismutase and Cancer” November 17th-21, , Orlando, Florida.
Invited University Lectures
University of Iowa , Northwestern University, University of Alabama, Birmingham , Yale University , University of Texas at San Antonio, University of Rochester, University of Louisville, Roswell Park, University of Kentucky, University of Pittsburgh , SUNY at Albany, Rensselaer Polytechnic Institute, University of Illinois, Union College, University of New Mexico, NYU, Oklahoma Medical Research Foundation , Drexel University.