• Primary Faculty Profiles
• Bankert, Richard, Ph.D., V.M.D., Professor
• Bianco, Piero, Ph.D., Associate Professor
• Campagnari, Anthony, Ph.D., Professor
• Collins, Arlene, Ph.D., Associate Professor
• Connell, Terry, Ph.D., Professor
• Egilmez, Nejat, Ph.D., Associate Professor
• Hakansson, Anders, Ph.D., Assistant Professor
• Hay, John, Ph.D., Professor and Chairman
• Jacobs, Amy, Ph.D., Assistant Professor
• Melendy, Thomas, Ph.D., Associate Professor
• Panepinto, John, Ph.D., Assistant Professor
• Read, Laurie, Ph.D., Professor
• Russell, Michael, Ph.D., Professor
• Ruyechan, William, Ph.D., Professor
• Thacore, Harshad, Ph.D., Associate Professor
• Williams, Noreen, Ph.D., Professor
• Adjunct Faculty Profiles
• Departmental Publications
• Career Opportunities
• The Witebsky Center
• Seminars

Faculty and Research

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Education:

2004 - 2008, Postdoc, Membrane Structure and Function Section, National Cancer Institute, Fort Detrick, MD

(Mentor: Robert Blumenthal)
2004, Ph.D., Biochemistry and Molecular Biology, University of Illinois at Chicago

(Mentor: Michael Caffrey)
1992, Bachelor of Arts, Comparative Literature and Italian, University of Iowa
1989 - 1990, Universita Cattolica del Sacro Cuore, Milan, Italy

 

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Research Interests:

The goal of our laboratory is to expand our knowledge of pathogen interactions with cellular membranes by developing a detailed understanding of virus entry into the cell. The mechanisms of host-microbe interactions also serve as templates for us for the design of novel drug delivery and gene therapy tools. We are dedicated to teaching and training and we work to foster the development of young scientists with an approach that is tailored to the individual.

Inhibition of HIV Entry: Kinetics and Mechanisms of Viral Membrane Fusion

• HIV entry inhibition
• membrane protein oligomerization and mobility
• inhibitors and antibodies as conformational probes
• binding and fusion

We develop inhibitors that interact with the HIV envelope proteins to halt the entry of the virus into cells. There are numerous small molecule and peptide inhibitors along with conformational antibodies that bind to the envelope proteins only at different stages during the recognition and fusion process. These inhibitors and antibodies can be used synergistically to attempt to design entry inhibitor cocktails and also to unveil further detail of the molecular mechanism of entry. The details of these stages in the entry process provide vital information from which we then design new and improved inhibitors that will be beneficial on both a therapeutic and a chemopreventive level.

Nanobiology

• virus mimicry
• membrane fusion protein reconstitution
• targeting cancer cells
• targeting viruses

We are developing innovative nanoparticles that deliver therapeutic agents directly into the cytosol of targeted cells utilizing direct membrane fusion with the plasma membrane. We are also targeting these systems to specific cell types by the addition of targeting moieties. It is projected that via this route of protein and nanoparticle engineering, it will be possible to target not only specific cells but to target specific organelles within cells such as the nucleus, Golgi apparatus or endoplasmic reticulum. This development will provide prospective treatments for diverse diseases from viruses to cancer and will also lead to the advancement of basic research in membrane proteins and membrane cellular biology.

Relevant references:

Fowler, A.L., Shah, K., Panepinto, J.C., Jacobs, A., Koffas, M.A.G. Antimicrobial drug discovery through chemical synthesis of non-natural flavanones. PLOS One [In Press] (2011).

Yi, H.Y., Panepinto, J.C., Jacobs, A. Inhibition of HIV entry by extracellular glucuronoxylomannan of Cryptococcus neoformans. Microbial Pathogenesis. Oct. 2 [Epub ahead of print] (2011).

Yi, H.A., Diaz-Aguilar, B., Bridon, D., Quraishi, O.,Jacobs, A. Permanent Inhibition of Viral Entry by Covalent Entrapment of HIV gp41 on the Virus Surface. Biochemistry.  Aug 16; 50 (32): 6966-72 (2011).

Huang, K., Jacobs, A., Rzayev, J. De Novo Synthesis and Cellular Uptake of Organic Nanocapsules with Tunable Surface Chemistry. Biomacromolecule.  Jun 13; 12(6): 2327-34 (2011).

Garg, H., Viard, M., Jacobs, A., Blumenthal, R. Lipophlic and Amphiphilic Interactions in Glycoprotein 41: Targets for Therapy; Current Topics in Medicinal Chemistry. In press, (April 2011).

Zielinski, R., Lyakhov, I., Jacobs, A., Chertov, O., Kramer-Marek, G., Francella, N., Stephen, A., Fisher, R., Blumenthal, R., Capala, J. Affitoxin-A Novel Recombinant, HER2-Specific, Anti-Cancer Agent for Targeted Therapy of HER2-Positive Tumors. Journal of Immunotherapy. Oct; 32(8):817-25 (2009).

Jacobs, A., Blumenthal, R. Understanding the Design Principles of Living Systems at the Nanoscale. Current Nanoscience 5 (1): 45-50(6) (2009).

 

Jacobs, A, Garg, H., Viard, M., Raviv, Y., Puri, A., Blumenthal, R. HIV-1 Envelope Glycoprotein-Mediated Fusion and Pathogenesis: Implications for Therapy and Vaccine Development. Vaccine. 26 (24): 3026-35 (2008)

Jacobs, A., Quraishi, O., Francella, N., Bridon, D., Blumenthal, R. A covalent inhibitor targeting an intermediate conformation of the fusogenic subunit of the HIV-1 envelope complex. J. Biol. Chem. 282 (44): 32406-13 (2007).

Sen, J., Jacobs, A., Jiang, H., Rong, L., Caffrey, M. The disulfide loop of gp41 is critical to the furin recognition site of HIV gp160. Protein Sci. 16 (6):1236-41 (2007).

Jacobs, A., Dimitrov, A.S., Finnegan, C.M.,Stiegler, G.,Katinger, H., Blumenthal, R. Exposure of the membrane-proximal external region of HIV-1 envelope glycoprotein-mediated fusion. Biochemistry. 280 (29):27284-8 (2005).

Jacobs, A., Simon, C., Caffrey, M. Thermostability of the HIV gp41 wild-type and loop mutations. Protein Pept. Lett. 13 (5): 477-80 (2006).

Jacobs A., Caffrey M. Alanine scanning mutants of the HIV gp41 loop. J. Biol. Chem. May 24 (2005).

Jacobs A., Hartman K, Laue T, Caffrey, M. Sedimentation velocity studies of the high-molecular weight aggregates of the HIV gp41 ectodomain. Protein Science. 13 (10): 2811-3 (2004).

Jiang S., Jacobs A., Laue T., Caffrey M. Solution structure of the coxsackievirus and adenovirus receptor domain 1. Biochemistry. 43 (7): 1847-53 (2004).

Gilhaudis L., Jacobs A., Caffrey M. Solution Structure of the HIV gp120 C5 Domain. Eur. J. Biochem. 269 (19): 4860-7 (2002).

Hakansson S., Jacobs A., Caffrey M. Heparin binding by the HIV-1 tat protein transduction domain. Protein Science. 10 (10): 2138-9 (2001).