Senior Research Scientist

Lautaro Gabriel Perez, Ph.D.

*** ****** *****, ***********, ** 27560

Phone 919-***-**** e-mail: *******@****.***

EDUCATION

Ph.D. 1987 University of Alabama at Birmingham, Birmingham, AL (Major: Microbiology)

BS, MS 1980 Catholic University of Chile, Santiago, Chile (Major: Microbiology)

RESEARCH AND PROFESSIONAL EXPERIENCE

2006-present Senior Research Associate, Laboratory of HIV Vaccine Development, Department of Surgery, Duke University Medical Center, Durham, NC. Studies aimed at defining the role of immunoglobulins Fc receptors in HIV neutralization. Development of assays and HIV envelope mutants to determine the induction of broadly neutralizing antibodies by vaccine candidates.

2001-2006 Research Scientist III, Howard Hughes Medical Institute, Department of Cell Biology, Duke University Medical Center, Durham, NC in collaboration with Oliver Smithies at University of North Carolina Chapel Hill to develop a mouse model to study HIV neutralization and vaccine development.

1997-2001 Associate Professor, Virology Program, Biomedical Sciences Institute, School of Medicine University of Chile, Santiago, Chile. Principal investigator of a project funded by the Chilean Scientific Comission, FONDECYT, aimed at defining the role of apoptosis in the CNS damage caused by HIV.

1994-1997 Associate Professor, Molecular Biology Graduate program, University of South Florida and Tampa Bay Research Institute, Tampa Florida. Principal Investigator of an NIH-funded project aimed to understand the process of viral entry using as a model human lentiviruses.

1990-1994 Assistant Professor, Department of Neurology and Microbiology. University of Minnesota Medical School, Minneapolis, MN. Principal Investigator of an NIH-funded project aimed to understand the process of viral entry using as a model human lentiviruses. Coprincipal investigator of a Program project aimed at understanding the possible toxicity of the HIV glycoprotein in the CNS.

1988-1990 Assistant Professor, Molecular Biology Division of the Retroviroly Laboratory. Mount Sinai Medical Center, Miami Beach, FL. Department of Biochemistry University of Miami, FL. Principal Investigator of an NIH-funded project aimed to study the process of Oligomerization of the HIV glycoproteins.

1986-1988 Postdoctoral fellow, I worked with Dr. Simon Wain-Hobson in the Laboratory of Retroviruses, Pasteur Institute, Paris, France. Cloning, sequencing and expression of HIV envelope genes from different African virus isolates.

1981-1986 Ph.D. student, Molecular and Cell Biology program, Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL. Mentor: Eric Hunter, Characterization of the Rous Sarcoma Virus envelope glycoprotein biosynthesis and processing, design of expression vectors and site-directed mutants.

HONORS & AWARDS

1981-1984 Odeplan-Chile graduate student scholarship

1986 SIGMA-XI Society, University of Alabama chapter, Graduate student award

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1986-1988 Weizman-Pasteur Postdoctoral fellowship

1994 CONICYT- Chile Visiting Professor fellowship

GRANT AWARDS

Oligomerization of the HIV Glycoproteins from The National Institute of Allergy and Infectious Diseases 5R29AI028566-05 PI: L.G. Perez, Start date 30-SEP-1989, End date: 30-JUN-1994.

AIDS Dementia Complex, Program Project, from the National Institute of Neurological Disorders and Stroke, NIH. Program Director R.W. Price. Project#6 Transgenic Mice Expressing HIV proteins. A model for the HIV-Induced Damage PI: L.G. Perez Start Date Sept 1992, End date June 1997.

HIV and the immune response of Chilean Infected Individuals, from CONICYT and the Swedish Agency Research Cooperation for Development Countries, SAREC. PI L.G. Perez. Dec1996-Dec1997.

Role of gp120-Induced Apoptosis in the AIDS Dementia Complex, from FONDECYT, Comision Nacional de Investigacion Cientifica y Tecnologica, CONICYT.Award# 1980852, PI L.G. Perez. Start Date March1998, End Date March 2001.

RESEARCH INTERESTS

I have been working with retroviral glycoproteins since my graduate school years. For my thesis project I characterized functional important regions of the Rous Sarcoma Virus envelope glycoproteins. I did one of the first studies using site-directed mutagenesis, to demonstrate the role of the transmembrane and cytoplasmic domains in biosynthesis, intracellular transport and viral assembly of an Env complex. Using similar studies, I characterized the proteolytic processing of the env precursor and define the critical residues for this event. This work resulted in four publications that are cited in many papers and Virology books (Perez et al., J. Virol.61, 66). For my postdoctoral training I went to the lab of Dr. L. Montangier at the Pasteur Institute in Paris. There I cloned, sequenced, and expressed the envelope proteins of HIV African isolates using vaccinia virus vectors. At the University of Miami and Mount Sinai Medical center, working as an independent investigator, I got my first NIH award to study the oligomerization of the HIV glycoproteins. Using chemical cross-linking and sucrose gradients I demonstrated that the Env is a heterotrimer composed of gp120 and gp41 subunits (Perez et al., AIDS Res.and Human Retrov.10).

Later, at the University of Minnesota, working with Richard Price a Neurologist that described the AIDS dementia complex, I had access to a HIV-1 brain isolate, YU2, which was cloned directly from the brain of an AIDS patient with a severe encephalopathy. I was the first to express the YU2 envelope glycoprotein and showed that in contrast to the glycoprotein of a lab-adapted strain, it didn’t cause cell fusion in a cell indicator assay. This clearly showed that there were other membrane components needed for that event, that turned out to be the CCR5

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coreceptor (Virology 215). More recently, I have been studying the role of Fc receptors on HIV neutralization. For that, I constructed lentiviral vectors encoding the human Fc receptors and

established indicator cell lines expressing the human IgG, IgA and IgM Fc receptors. We have shown that the high affinity FcγRI receptor can dramatically increase the neutralization capacity of human antibodies directed to the gp41 MPER region and nearby regions. This FcγRI effect on MPER mAbs can be seen with viruses from different clades and tiers (J.Virol.83). The FcγRI cell line has been very useful to characterize new MPER monoclonal antibodies and has been used by other groups to study ADCC as well. More recently, I have developed assays to study the role of the integrins α4β7 in HIV infectivity and the role of complement in the partial protection observed in the vaccine trial RV144. Currently we are studying the envelope modifications required to elicit broadly neutralizing antibodies the most challenging aspect of producing a protective HIV vaccine.

PUBLICATIONS

Perez, L.G., Wills, J.W., and E. Hunter. 1987. Expression of the Rous Sarcoma virus env gene from a simian virus 40 late- replacement vector: effect of upstream initiator codons. J. Virol.61:1276-1281

Perez, L.G. and E. Hunter 1987. Mutations within the proteolytic cleavage site of the Rous Sarcoma virus glycoprotein precursor block processing to gp85 and gp37. J. Virol.61: 1609-1614.

Perez, L.G., Davis, G.L. and E. Hunter. 1987. Mutants of the Rous Sarcoma Virus envelope glycoproteins that lack the transmembrane and/or cytoplasmic domains: Analysis of intracellular transport and assembly into virions. J. Virol.61: 2981-2988.

Perez, L.G. Lorenzo,E., and L. Resnick. 1989. Oligomerization of the Human Immunodeficiency virus envelope glycoproteins. AIDS Res. and Human Retroviruses 10 (5): 567-573.

Perez, L.G. O’Donnell, M.A., and E. B. Stephens.1992. The transmembrane glycoprotein of the human immunodeficiency virus type I induces syncytium formation in the absence of the receptor binding subunit. J. Virol. 66: 4134-4143.

Dong, Jianyun, Dubay, John W., Perez, L.G., and E. Hunter. 1992. Mutations within the proteolytic cleavage site of the Rous Sarcoma virus glycoprotein define a requirement for dibasic residues for intracellular cleavage. J. Virol. 66: 865-874.

Li,Y.Y., O’Donnell, M.A., and L.G. Perez. 1996. Coexpression of a non-syncytium inducing HIV-1 envelope glycoprotein blocks the syncytium-inducing capacity of another env gene product. Virology 215: 197-202.

Li,Y.Y., and L.G. Perez. 1997. The entire SU/gp120 subunit of the HIV-1 is required for the incorporation of the glycoprotein complex into virions. Virus Genes 14: (3) 211-223.

L.G. Perez. 2000. The molecular biology of HIV and the recent progress in the treatment of AIDS. Review article. Rev. Chil. Pediatr .7: (2) 83-88.

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Perez, L.G. Todd, C.A., and D.C. Montefiori. 2008. Enhanced neutralization of HIV-1 by gp41 MPER-specific antibodies in cells that express Fcγ Receptors. Abstract AIDS Res. Human Retroviruses 24(1): 1-40.

Perez, L.G., Costa, M.R., Todd, C.A., Haynes, B.A., and D.C. Montefiori. 2009. Utilization of immunoglobulin G Fc Receptors by human immunodeficiency virus type 1: a specific role for antibodies against the membrane-proximal external region of gp41. J. Virol. 83:7397-7410.

Tang, H., Robinson, J.E., Gnanakaran, S., Li,., Rosenberg, E.S., Perez, L.G., Haynes, B. F., Liao, H-X., LaBranche, C.C., Korber, B.T., and D. C. Montefiori. 2011.

Epitopes immediately below the base of the V3 loop of gp120 as targets for the initial autologous neutralizing antibody response in two HIV-1 subtype B-infected individuals.

J. Virol. 85:9286-9299.

Perez, L.G., Zolla-Pazner S., and D.C. Montefiori. 2013. Mechanism of Antibody-Dependent FcγRI-Mediated Neutralization of HIV-1 in TZM-bl Cells. J. Virol. 87:5287-5290.

Sarzotti-Kelsoe M., Daniell L. Todd C.A., Bilska M., Martelli A., LaBranche C., Perez L.G., Ochenbauer C., Kappes J.C., Rountree W., Denny T.N., and D.C. Montefiori. 2014. Optimization and Validation of a Neutralizing Antibody Assay for HIV-1 in A3R5 Cells. J. Immunol. Meth. 409:147-160.

Perez, L G., H. Chen, H-X Liao, and D.C. Montefiori. 2014. Envelope Glycoprotein Binding to the ɑ4β7 Integrin Complex is not a General Property of Most HIV-1 Variants. J. Virol. 88:107**-*****.

Perez, L.G., Martinez, D, decamp, A.C., Pinter, A., Berman, P.W., Francis, D., Faruk Sinangil, S., Lee, C., Greene,K., Gao, H., Nitayaphan, S., Rerks-Ngarm, S., Kaewkungwal, J., Pitisuttithum, P., Tartaglia, J., O’Connell, R.J., Robb, M.L., Michael, N.L., Kim, K.H., Gilbert, P., and D. C. Montefiori. 2017. V1V2-Specific Complement Activating serum IgG as a Correlate of HIV-1 Infection Risk in RV144. PLoS ONE 12(7):e0180720

LaBranche, CC., McGuire, AT., Gray, MD., Berhens, S., Zhou, T., Sattentau, Q.J., Peacock, J., Eaton, A., Greene, K., Gao, H., Tang, H., Perez, L.G., Saunders, K.O., Mascola, J.R., Haynes B.F., Stamatatos, L., and D.C. Montefiori. 2018. HIV-1 Envelope Glycan Modifications that Permit Neutralization by Germ-line-Reverted VRC01-Class Broadly Neutralizing Antibodies. PLoS Pathog. 14(11):e1007431

Tay, M.Z. Kunz, E.L., Deal, A., Zhang, L., Seaton, K.E., Rountree, W., Eudailey, J.A. Heptinstall, J., McRaven, M.D., Matias, E., McGuire E., Yates, N.L., Perez, L.G., Montefiori, D.C., Overman, R.G., Hope, T.J., Shen, X., Kalilani, L., Fouda, G.D., Tomaras, G.D., and S.R. Permar. 2019. Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in HIV-1 Chronically Infected Women. J.Virol. 93:e02084-18. doi: 10.1128/JVI.02084-18

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LaBranche, CC., Henderson, R., Hsu, A., Behrens,S., Chen, X., Zhou, T., Wiehe, K., Saunders, KO., Alam,SM., Bonsignori, M., Borgnia, MJ., Sattentau, QJ., Eaton, A., Greene, K., Gao, H., Perez, LG., Edwards, RJ., Kepler, TB., Korber, BT., Kwong, PD., Mascola, JR., Acharya, P., Haynes, BF.,and D.C. Montefiori. 2019. Neutralization-guided design of HIV-1 envelope trimers with high affinity for unmutated common ancestor of the CH235 lineage of CD4 binding site broadly neutralizing antibodies. PLoS Pathog. In press.

Ringe, R. P., Cruz Portillo, V. M., Dosenovic, P., Ketas,T., Ozorowski,G., Nogal, B., Perez, L.G., LaBranche, C., Lim, J., Francomano, E., Wilson, I.A., Sanders,R.W., Ward, A.B., Montefiori, D.C., Nussenzweig, M.C., Klasse, P.J., Cupo, A., and J. P. Moore. 2019. Neutralizing antibody induction by HIV-1 Envelope glycoprotein SOSIP trimers on iron oxide nanoparticles may be impaired by mannose binding lectin. J. Virol. Submitted.

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