University Home | Hospital | Pulse Employment | Contact Us | Search | News 
Thomas Jefferson University Search Jefferson
Jefferson Medical College Jefferson College of Graduate Studies Jefferson College of Health Professions
Menu
Thomas Jefferson University - Teresa Fernandes-Alnemri, PhD
Teresa Fernandes-Alnemri, PhD

Biochemistry & Molecular Biology
Thomas Jefferson University
Jefferson Medical College
Department of Biochemistry & Molecular Biology
Research Assistant Professor
Mailing Address
233 S. 10th Street, BLSB 902
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-4631
t_alnemri@mail.jci.tju.edu
Qualifications
Ph.D., Thomas Jefferson University, Genetics, 1994
Expertise and Research Interests
The research in my lab focuses on the signaling pathways involved in caspase-1 activation and pro-inflammatory cytokine production by members of the NLR family including NLRP1, NLRP3, NLRC4, NOD1 & NOD2, and the interferon-induced protein AIM2 (absent in melanoma 2).
We are interested in how NLR proteins and other cytosolic danger sensors such as AIM2 can recognize microbial pathogen- and tissue damage-derived molecular danger signals, and assemble inflammasome complexes. These complexes serve as molecular platforms to recruit and activate procaspase-1 to produce the active caspase-1, which processes pro-IL-1² and pro-IL-18 into their corresponding mature pro-inflammatory cytokines, IL-1² and IL-18.

Although pro-inflammatory cytokine production is an innate immune response important for protection against infections with different pathogens, abnormal or chronic activation of the pro-inflammatory innate immune system could lead to a wide variety of digestive diseases such as Crohns disease and autoimmune disorders afflicting the kidney, like systemic lupus erythematosus. Chronic inflammatory responses have also been implicated in anemia of inflammation and chronic disease (AI/ACD). Some of the diseases that could lead to AI/ACD include rheumatoid arthritis, lupus, diabetes, heart failure, degenerative joint disease, kidney diseases, cancer and inflammatory bowel disease (IBD) including Crohns disease.

We also recently demonstrated that the interferon-inducible AIM2 protein functions in cytosolic surveillance of cytoplasmic dsDNA, which is produced as a consequence of infection with viral and bacterial pathogens. Activation of the AIM2 inflammasome by binding to cytosolic dsDNA results in proinflammatory cytokine production. We have generated AIM2 knock out mice, and successfully used our model system to demonstrate that AIM2 is the innate sensor of pathological DNA complexes formed when cells are infected with dangerous pathogens like the 'rabbit fever' bacteria Francisella, and viruses such as the poxvirus Vaccinia.
Because activation of AIM2 by DNA triggers a strong inflammatory response, we are actively investigating whether the antibody-DNA complexes found in systemic lupus erythematosus (SLE) are in fact recognized by AIM2. Lupus nephritis, is an inflammatory renal disease that often results in kidney failure in SLE patients. Understanding the molecular pathways that modulate these inflammatory responses in lupus patients would be paramount to designing effective therapeutics.
Keywords
Apoptosis; cell death; CPP32; Caspase; Pyrin; Nalp3; Inflammation; Inflammasome; Innate immunity; Caspase-1; Pyroptosis; Pyroptosome; ASC; AIM2; lupus;
Publications
  • Fernandes-Alnemri, T., Litwack, G. and Alnemri, E.S. CPP32: a novel human apoptotic protein with homology to C. elegans cell death protein CED-3 and mammalian interleukin-1b converting enzyme. J. Biol. Chem. 269, 308761-30764.1994
  • Alnemri, E.S., Fernandes-Alnemri, T. and Litwack, G. Cloning and expression of four novel isoforms of human interleukin-1 b converting enzyme with different apoptotic activities. J. Biol. Chem. 270, 4312-4317. 1995
  • Fernandes-Alnemri, T., Armstrong, R., Krebs, J., Srinivasula, S.M., Wang, L., Yu, Z., Trapani, J.A., Tomaselli, K. J., Litwack, G., and Alnemri, E.S. Activation of CPP32 by Mch4, A Novel Human Apoptotic Cysteine Protease containing two FADD-like Domains. Proc. Natl. Acad. Sci. USA. 93, 7464-7469. 1996
  • Srinivasula, S.M., Ahmad, M., Fernandes-Alnemri, T., Litwack, G. and Alnemri, E.S. Molecular ordering of the Fas-apoptotic pathway: The Fas/Apo-I protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proc. Natl. Acad. Sci. USA. 93, 13706-13711 1996.
  • Srinivasula, S.M., Ahmad, M., Fernandes-Alnemri, T., and Alnemri, E.S. Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. Mol. Cell 1:949-957. 1998.
  • Srinivasula, S.M., Ahmad, M., Lin, J-H., Poyet, J.L., Fernandes-Alnemri, T., Tsichlis, P.N. and Alnemri, E.S. CLAP, a novel CARD-containing Protein in the TNF-receptor Pathway, Regulates NF-kappa B Activation and Apoptosis. J. Biol. Chem. 274, 17946-17954. 1999.
  • Qin, H., Srinivasula, S.M., Wu, G., Fernandes-Alnemri, T., Alnemri, E.S., and Shi, Y. Structural basis of procaspase-9 recruitment by the apoptotic protease activating factor (Apaf-1). Nature. 399:549-557. 1999.
  • Srinivasula, S.M., Hegde, R., Saleh, A., Datta, P., Shiozaki, E., Chai, J., Lee, R.A., Robbins, P.D., Fernandes-Alnemri, T., Shi, Y., Alnemri, E.S. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature, 410, 112-116. 2001
  • Poyet, J-L., Srinivasula, S.M., Tnani, M., Razmara, M., Fernandes-Alnemri, T., Alnemri, E.S. Identification Of Ipaf, A Human Caspase-1 Activating Protein Related To Apaf-1. J. Biol. Chem. 276(30):28309-28313. 2001.
  • Hegde, R., Srinivasula, S.M., Zhang, Z., Wassell, R., Mukattash, R., Cilenti, L., DuBois, G., Lazebnik, Y., Zervos, A.S., Fernandes-Alnemri, T., Alnemri, E.S. Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem. 277(1):432-8. 2002
  • Jones, J.M., Datta, P., Srinivasula, S.M., Ji, W., Gupta, S., Zhang, Z., Davies, E., Hajnoczky, G., Saunders, T.L., Van, Keuren, M.L., Fernandes-Alnemri, T., Meisler, M.H. and Alnemri, E.S. Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice. Nature. 425(6959):721-7 2004.
  • Yu, JW., Wu,J., Zhang,Z., Datta,P., Ibrahimi,I., Taniguchi,S., Sagara,J., Fernandes-Alnemri,T., Alnemri,E.S. 2006 Cryopyrin and Pyrin activate caspase-1, but not NF-kB, via ASC oligomerization. Cell Death and Differentiation, 13(2):236-49, 2006.
  • Fernandes-Alnemri T, Wu J, Yu JW, Datta P, Miller B, Jankowski W, Rosenberg S, Zhang J, Alnemri ES.The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death & Differentiation 14(9):1590-604, 2007.
  • Yu, JW., Fernandes-Alnemri T, Datta P., Wu J., Juliana,C., McCormick, M., Solorzano, L., Zhang. Z., Alnemri, E.S. 2007 Pyrin activates the ASC Pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol. Cell 28(2):214-27, 2007
  • Khan F., Fujioka, M., Datta, P., Fernandes-Alnemri, T., Jaynes, J. B., and Alnemri E. S. Drosophila Omi/HtrA2 targets the BIR1-Linker domain to inactivate DIAP1. Cell Death and Differentiation 15, 1073-1083, 2008.
  • Fernandes-Alnemri, T. and Alnemri E. S. Assembly, purification and assay of the activity of the ASC pyroptosome. Methods Enzymol. 442, 251-270, 2008.
  • Fernandes-Alnemri, T., Yu, J-W, Datta, P., Wu, J. and Alnemri, ES. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458: 509-513, 2009 AOP Jan 21, 2009
  • Juliana C, Fernandes-Alnemri T, Wu J, Datta P, Solorzano L, Yu JW, Meng R, Quong AA, Latz E, Scott CP, Alnemri ES. The anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J Biol Chem.Jan 21. 2010 (Epub)
  • Fernandes-Alnemri T., Yu JW., Juliana, C., Solorzano, L., Kang, K., Wu, J., Datta, P., McCormick, M., Huang, L., McDermott, E., Kastner, D., Eisenlohr, LC., Laandel, C., and Alnemri, E. (2010) The AIM2 inflammasome is critical for innate immunity against F.tularensis. Nat Immunol. 2010 May;11(5):385-93. Epub Mar 28,2010.

Individual Expertise profile of Teresa Fernandes-Alnemri, PhD, Copyright © Teresa Fernandes-Alnemri, PhD.
Last Updated by Admin : Tuesday, June 5, 2012 3:43:41 PM



 Printable Version

Thomas Jefferson University
Thomas Jefferson University