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Early Career Investigator Recognition

October 2012

 

Laura Pattacini, Ph.D.

Fred Hutchinson Cancer Research Center, US
Nominated by Dr. Julie McElrath

Laura Pattacini is a postdoctoral research fellow in the Lund Lab, in the Vaccine and Infectious Diseases Division at the Fred Hutchinson Cancer Research Center. She received her PhD in Clinical and Experimental Hematology at the University of Bologna in 2004 and a specialty degree in Clinical Biochemistry at the University of Parma in 2008.

Her main research focus is investigating the role of T cells and regulatory T cells in protection from HIV infection. She collaborated with the CAVD on a project aimed at using a mouse model to test the immunogenicity of a novel HIV vaccination strategy consisting of a prime-boost using Env CN54 protein adjuvanted by the TLR agonist IC31, and boosting with NYVAC-CN54, as provided by Dr Giuseppe Pantaleo at the University of Lausanne. The results of this study, showing the advantages of using IC31 as compared to alum in the vaccination, have been recently published in PLoS ONE. Laura is currently testing other TLR agonists and conducting a comparative study to determine the most efficacious adjuvant to induce a durable and broad T cell and antibody response both systemically as well as at mucosal sites.

September 2012

 

Laura McCoy, Ph.D.

University College London, UK
Nominated by Dr. Robin Weiss

Laura McCoy is a Postdoctoral Researcher at University College London (UCL), UK working with Prof. Robin Weiss. She completed her undergraduate studies in Biochemistry at the University of Oxford, UK in 2004 and received her PhD degree in 2010 from Imperial College London, UK. After joining Prof. Weiss’s group in 2010, Laura developed a novel screening method that led to the isolation of a potently neutralizing llama heavy-chain only antibody variable region (VHH) J3 from a llama immunized with HIV envelope proteins.

In collaboration with the group of Prof. Theo Verrips in the Netherlands and Mike Seaman at the CA-VIMC, Laura demonstrated that J3 neutralizes 96% of strains including subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. The breadth and potency of J3 is much improved compared to the anti–HIV antibodies previously isolated after immunization, including but not limited to other llama VHH. A high-throughput robotic platform has been used to isolate additional potent neutralizing VHH. Like J3, these VHH also target the CD4-binding site but neutralize viruses which are resistant to J3, highlighting the diverse ways this conserved region is susceptible to antibodies. Llama-human fusion antibodies have been constructed, demonstrating that the neutralization ability of J3 is not solely a function of the small size of the VHH as the fusion antibody (full-length but heavy-chain only) shows enhanced potency. With collaborators in Europe, Laura is assessing the ability of a J3-containing vaginal microbicide to protect against SHIV challenge in the rhesus macaque model.

July 2012

 

Craig Pace, Ph.D.

Aaron Diamond AIDS Research Center, US
Nominated by Dr. David Ho

Craig Pace is a Research Scientist at the Aaron Diamond AIDS Research Center (ADARC) working with Dr David Ho. He received his BSc(Hons) (2001) and PhD (2006) degrees in Australia from Murdoch University investigating mechanisms of HAART-associated lipodystrophy and characterizing APOBEC3-mediated hypermutation at population level in vivo, respectively, under the mentorship of Dr Simon Mallal at the Center for Clinical Immunology and Biomedical Statistics. Since joining Dr Ho’s lab as a post-doc in 2007, Craig’s research has focused on characterizing ibalizumab’s anti-HIV-activity, mechanisms of resistance and the development of second generation ibalizumab molecules with improved breadth and potency.

Working with others in the lab and with Mike Seaman at the CA-VIMC, Craig demonstrated ibalizumab’s broad and potent anti-HIV-activity against a large panel of clinically-relevant Env pseudoviruses and characterized genetic determinants of resistance. Following the characterization of ibalizumab’s breadth and potency, Craig initiated the development bispecific versions of ibalizumab in order to improve its antiviral activity. These antibody-like molecules exploit ibalizumab’s demonstrated safety and efficacy to anchor and thereby concentrate the activity of broadly neutralizing Env-directed antibodies at the site of viral entry. The most impressive construct, PG9-iMab, a bispecific antibody comprised of PG9 and ibalizumab moieties, was able to neutralize 100% of a large pseudovirus panel at picomolar concentrations, in both the TZM-bl and PBMC assays, significantly better than either PG9 or ibalizumab, either alone or in combination. Currently, Craig is assessing PG9-iMab’s pharmacokinetic profile and ability to protect against SHIV challenge in the rhesus macaque model.

June 2012

 

Shaunna Shen, D.V.M., Ph.D.

Duke University Medical Center, US
Nominated by Dr. David Montefiori

Shaunna Shen is a Medical Instructor in the Department of Medicine at Duke University Medical Center working with Dr. Georgia Tomaras. She received her DVM training in China Agricultural University (Beijing, China) in 1995 and her PhD in Comparative Pathology from University of California at Davis in 2004. Her graduate research focused on evaluation of a live-attenuated feline immunodeficiency virus (FIV) vaccine in cats.

Dr. Shen’s current main research interest is characterization of antibody responses, with a new focus on non-human primate and small animal models. She helped develop/optimize the peptide array technology for mapping of HIV/SIV-specific linear epitopes targeted by antibodies following infection/vaccination. She has further optimized the technology for use in characterizing monoclonal antibodies and antibody responses in NHP and small animal models. Another research interest of Dr. Shen is the examination of mucosal responses. She heads the efforts in Dr. Tomaras’ group in IgA isolation and related characterization of these antibodies. Dr. Shen was awarded a CHAVI/HVTN early stage investigator grant in 2011 to compare binding antibody responses in NHP and in human following immunization with a comparable immunogen.

Currently, Dr. Shen leads the effort in expanding the peptide microarray linear epitope mapping technology to more animal models, and for evaluation of different antibody isotypes. In addition, she plans to explore the application of the binding antibody multiplex assay (BAMA) in more animal models, for more extensive evaluation of antibody responses from NHP and small animal studies.

May 2012

 

Paul McLaren, Ph.D.

Broad Institute of MIT and Harvard, US
Nominated by Dr. Bruce Walker

Dr Paul McLaren is an affiliate member of the Broad Institute of MIT and Harvard working with Dr Paul de Bakker. He received his Bachelor’s degree in Genetics from the University of Manitoba. Dr McLaren’s graduate research focused on transcriptional profiling, gene-network analysis and immune function in HIV exposed, uninfected individuals for which he received his PhD in 2008.

As a member of the Walker VDC, Dr McLaren’s primary research focus is on identifying common and rare host genetic variants that contribute to durable control of HIV viremia. He was the co-leader of the analysis team that performed the genome-wide association study in 1,000 HIV controllers and 2,500 progressors. This study identified five variable amino acid positions in the HLA-B peptide binding groove that explain the known classical HLA allele and SNP associations in controllers of European ancestry. More recently, Dr McLaren extended this work to African American controllers/progressors, identifying a variable amino acid position outside of the binding groove (not present in the European sample) that also contributes to HIV control.

Currently, Dr McLaren’s work leverages next-generation sequencing technologies to obtain information on all classes of genetic variation in a set of candidate genes and exome-wide (i.e. all coding exons). The goal of this work is to evaluate, alone and in bulk, the contribution of rare variants to HIV control.

April 2012

 

Mattia Bonsignori, MD, Ph.D.

Duke University Medical Center, US
Nominated by Dr. Bart Haynes

Mattia Bonsignori is a Medical Instructor in the Department of Medicine at Duke University Medical Center and a Faculty member of the Duke Human Vaccine Institute, where he currently directs the operations of the Laboratory of B cell Repertoire Analysis. He received his M.D. (2001) and specialization degree in Clinical Microbiology and Virology (2005) at University of Insubria (Varese, Italy). A prior postdoctoral research associate in the Department of Immunology at St. Jude Children’s Research Hospital (Memphis, Tennessee, USA), where he worked on an experimental HIV-1 vaccine in Dr. Julia Hurwitz laboratory and in collaboration with Dr. Peter Doherty and Dr. Karen Slobod, he joined Dr. Haynes laboratory at the Duke Human Vaccine Institute in December 2005.

Dr. Bonsignori’s research focuses on the analysis of the memory B cell repertoire in HIV-1-infected individuals and vaccine recipients. He developed a limiting dilution memory B cell culture system for the expansion and high-throughput screening of single memory B cells from peripheral blood and mucosal samples. By applying this method, he identified and characterized a clonal lineage of V1/V2 conformational epitope-specific broadly neutralizing antibodies and their unmutated common ancestors (Bonsignori et al., J Virol 2011; 85(19):9998-10009). In that work, he demonstrated that the unmutated common ancestors, albeit displaying restricted neutralizing activity, retained the ability to bind to a gp120 HIV-1 envelope glycoprotein with an affinity predicted to trigger B cell development, thus identifying potential immunogen candidates capable to initiate the antibody maturation toward the development of V1/V2 conformational epitope-specific antibodies with broad neutralization.

More recently he has applied the same strategy to probe the repertoire of memory B cells with anti-HIV-1 activity from participants in the RV144 HIV-1 vaccine efficacy trial.

March 2012

 

Michael Seaman, Ph.D.

Beth Israel Deaconess Medical Center, Harvard Medical School, US
Nominated by Dr. David Montefiori

Dr. Michael Seaman is an Assistant Professor in Medicine at Beth Israel Deaconess Medical Center, Harvard Medical School. He obtained his Ph.D. in Immunology from the University of Texas Southwestern Medical Center in 2000, and did his post-doctoral research training with Dr. Norman Letvin at Harvard Medical School where he studied the use of cytokine adjuvants for augmenting HIV vaccine-elicited T cell responses in non-human primates.

Since 2006, Dr. Seaman has directed the CAVD Pre-Clinical Neutralizing Antibody Core Laboratory as part of the Comprehensive Antibody Vaccine Immune Monitoring Consortium (CA-VIMC), under the direction of Dr. David Montefiori. His laboratory collaborates with numerous CAVD investigators by providing standardized assessments of neutralizing antibody responses to HIV-1, SIV, and SHIV viruses. These include, in part, the assessment of antibody responses elicited by candidate HIV-1 vaccines in small animal or non-human primate models, the screening of HIV+ patient cohorts to identify potent neutralizers, and the phenotypic assessment of novel monoclonal antibodies being developed by VDC investigators for their breadth and potency of neutralizing activity. To date, Dr. Seaman’s laboratory has conducted approximately 80,000 neutralizing antibody assays for 71 registered CAVD studies. Within the CA-VIMC, Dr. Seaman’s laboratory has also been extensively involved in the Standard Virus Panel Consortium, which has developed >500 novel HIV-1 Env pseudovirus strains from diverse genetic subtypes for use in standardized neutralization assays. In addition his lab participates in CA-VIMC Research and Development Program projects, the Specimen Acquisition Laboratory, and the Neutralization Serotype Discovery Project.

February 2012

 

Marina Caskey, Ph.D.

The Rockefeller University, US
Nominated by Drs. Sarah Schlesinger and Michel Nussenzweig

Dr. Caskey's research is focused on the development and clinical testing of HIV vaccines and vaccine adjuvants, particularly vaccines that work by directly targeting infectious antigens to dendritic cells.

Dendritic cells are the sentinels of the immune system. In the steady state, dendritic cells capture and process antigens, travel to lymphoid tissues and present the processed antigen to T cells, stimulating a robust immune response. Dr. Caskey is a member of the Steinman laboratory, which is developing a novel vaccine strategy that exploits this pivotal role of dendritic cells (DCs) in initiating adaptive immunity. Synthetic HIV proteins are fused to a monoclonal antibody that binds to an uptake receptor, DEC-205, that is primarily expressed on dendritic cells. In order to elicit immune responses, dendritic cells need to be in a mature state when antigen is delivered within the anti- DEC-205 antibody. A key component of our protein vaccine platform is the use of a vaccine adjuvant, such as poly ICLC, in combination with the anti-DEC-205 fusion antibody in order to induce maturation of dendritic cells.

Dr. Caskey has worked closely with other members of the laboratory to characterize the immunogenicity of the anti-DEC-205 p24 mAb vaccine construct in mice. When compared with other vaccine strategies in mice, anti-DEC205 HIV gag fusion antibody in combination with poly ICLC, as an adjuvant, induced stronger T cell immunity both in quantity and quality. These preclinical studies helped design the first-in-human concept study to test this novel dentritic cell-targeted HIV vaccine.

The first proof-of-concept trial of anti-DEC-205 p24 vaccine candidate is currently enrolling healthy volunteers at the Heilbrunn Outpatient Research Center of the Rockefeller University Hospital. Together with Dr. Schlesinger, Dr. Caskey evaluates and follows volunteers as they enroll in the trial. In the laboratory, Dr. Caskey will study the immune responses generated by this DEC-targeted HIV gag vaccine. If successful, this vaccine approach will add to the current arsenal of HIV vaccine strategies.

In order to understand, in humans, the mechanism whereby poly ICLC enhances T and B cell immunity, Dr. Caskey and colleagues carried on a phase I study to test the safety and early immune responses induced by poly ICLC. She found that poly ICLC reliably induces a systemic type-I IFN response when administered subcutaneously to healthy volunteers. This early IFN signature might correlate with the effectiveness of poly ICLC as a vaccine adjuvant. Future studies will continue to address the mechanism whereby poly ICLC and other adjuvants exert their immunomodulatory efffects in humans.

Prior to coming to the Rockefeller University, Dr. Caskey attended medical school at the Federal University of Sergipe in Brazil, she then completed her internal medicine residency at Saint-Lukes Roosevelt Hospital in New York, followed by fellowship training in Infectious Diseases at New-York Presbyterian Hospital (Cornell). Upon completion of medical training she joined the Laboratory of Cellular Physiology and Immunology, headed by Dr. Ralph Steinman, as a clinical scholar from 2006-2009. In 2009 she was awarded a Master.s degree in Clinical and Translational Research. She is now an Assistant Professor of Clinical Investigation at the Rockefeller University. Dr. Caskey is funded through a Career Development Award from the National Institutes of Health.

 

 

2016 Early Career Investigators

To view the honorees that occured in 2016, click the following link: 2016 Early Career Investigators

2015 Early Career Investigators

To view the honorees that occured in 2015, click the following link: 2015 Early Career Investigators

2014 Early Career Investigators

To view the honorees that occured in 2014, click the following link: 2014 Early Career Investigators

2013 Early Career Investigators

To view the honorees that occured in 2013, click the following link: 2013 Early Career Investigators

2012 Early Career Investigators

To view the honorees that occured in 2012, click the following link: 2012 Early Career Investigators

2011 Early Career Investigators

To view the honorees that occured in 2011, click the following link: 2011 Early Career Investigators

2010 Early Career Investigators

To view the honorees that occured in 2010, click the following link: 2010 Early Career Investigators

2009 Early Career Investigators

To view the honorees that occured in 2009, click the following link: 2009 Early Career Investigators

 
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