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Early Career Investigator Recognition

October 2013

 

Louise Scharf, Ph.D.

California Intitute of Technology, US
Nominated by Dr. Pamela Bjorkman

Dr. Louise Scharf is a post-doctoral fellow working on projects related to the Bjorkman CAVD at the California Institute of Technology. Dr. Scharf received her PhD in 2010 from the University of Chicago in Biochemistry and Molecular Biology and her B.S. in Finance from Cal State Northridge in 2006. For her PhD thesis, Louise solved the crystal structure of CD1c, a member of the CD1 family of lipid antigen-presenting proteins, which had resisted crystallization in the hands of many experienced structural biologists. Her interest in HIV started as an undergraduate, when she worked on identifying chemokine receptor-binding peptides that block entry of HIV1 and HIV-2.

As part of the Bjorkman CAVD, she has made significant advances in understanding broadly neutralizing anti-HIV antibodies and attempts to elicit them by vaccination. She uses a combination of X-ray crystallography, structural analyses and biochemistry/biophysical techniques to characterize antibody recognition of the HIV spike trimer. Her first set of structural studies (Mouquet*, Scharf* et al., 2012, Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. PNAS Plus 47: E3268-77) involved anti-HIV antibodies in the family of PGT121, a broadly neutralizing antibody whose epitope involves glycans on the V3 loop of gp120. Louise's crystal structures and associated biochemical characterizations uncovered the surprising result that PGT121 recognizes complex-type N-glycans; her studies represented the first structural/biochemical characterization of HIV epitopes involving complex-type carbohydrates. In a second paper (Scharf et al., 2013, Structural basis for HIV-1 gp120 recognition by a germ-line version of a broadly neutralizing antibody. PNAS 110:6049–54), Louise described the structure of a VH1-2*02-derived germ-line antibody heavy chain and its recognition of the CD4 binding site on HIV gp120. Comparison of the germ-line and mature antibody complexes with gp120 provides a roadmap for how HIV-specific B-cells are triggered by gp120 and suggests how antigens might be designed to elicit such antibodies. Louise continues to make exciting progress in the antibody-HIV field, having solved new structures of germ-line CD4 binding site antibody/gp120 complexes and is working towards understanding how germ-line versions of V3-loop antibodies are triggered by HIV.

June 2013

 

Neal Padte, Ph.D.

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

Dr. Neal Padte is the Project Manager for the Ho CAVD Consortiums and is Associate Director of Product Development at the Aaron Diamond AIDS Research Center (ADARC). Dr. Padte received his Ph.D. in Cellular, Molecular and Biophysical Studies from Columbia University in 2009 and his B.A. in Molecular Biology and Biochemistry from Boston University in 2000. His graduate studies identified and characterized novel cellular factors involved in cell polarity during cytokinesis. Prior to joining ADARC in 2009, Dr. Padte was a technology transfer specialist with Columbia Technology Ventures, assessing the scientific and commercial potential of a range of biologic and engineering technologies at Columbia University. His previous laboratory experience also includes HIV clinical trials research at ADARC and single molecule DNA sequencing technology development at GE Healthcare Life Sciences.

At ADARC, Dr. Padte currently manages the day-to-day activities of their CAVD consortiums’ preclinical and clinical development pipeline under the leadership of Dr. David Ho. This includes contributing to the scientific design of preclinical and clinical studies; drafting regulatory documents for IND, IACUC and IRB submissions; identifying and overseeing the performance of CMOs and CROs; and managing timelines and budgets for all scientific and clinical activities.

Most recently, Dr. Padte served as technical lead in preparation for the Ho: Enhancing Innate Immune Activation consortium’s pre-IND meeting for first-in-human evaluation of a novel glycolipid vaccine adjuvant, 7DW8-5. He also served as project manager for the Ho: Ibalizumab for HIV Prevention consortium’s Phase 1 clinical trial evaluating the mAb ibalizumab in healthy volunteers and is helping to advance this program towards Phase 2a study. Dr. Padte is also part of the strategic team managing the Ho: Engineered Bispecific bNabs for Prevention consortium’s discovery and preclinical development program that aims to identify next generation broadly neutralizing antibodies with exceptional potency against HIV-1 and develop a lead candidate for Phase 1 evaluation.

April 2013

 

Anthony P. West, Ph.D.

California Institute of Technology, US
Nominated by Dr. Pamela Bjorkman

Dr. Anthony West is the Project Manager for the Bjorkman CAVD and a Member of the Professional Staff at the California Institute of Technology. Dr. West received his PhD in physical organic chemistry from Caltech in 1998 and his B.A. in Chemistry from Princeton University in 1991. His graduate studies involved quantum orbital calculations on cation-pi interactions.

Dr. West joined the Bjorkman group as a post-doctoral fellow in 1998, where he worked on numerous structural biology projects using X-ray crystallography and other biophysical techniques. In 2005, he led the Bjorkman group effort to "Engineer Immunity" against HIV, a collaborative effort with David Baltimore's group that was funded by the Grand Challenges program of the Bill and Melinda Gates Foundation. As part of this effort and Leo Stamatatos' CAVD project, Dr. West designed and engineered more potent versions of HIV antibodies. His successful constructs and studies included characterization of a 2G12 dimer, an HIV carbohydrate-specific antibody that spontaneously dimerizes into a more potent form, and CD4 fusions with CD4-induced antibodies. More recently, Dr. West used bioinformatic and structural information to define a sub-class of antibodies that bind to the CD4 binding site on HIV-1 gp120. These studies identified signature features that rationalize the common germline origin of this class of broadly neutralizing antibodies and common routes of mutation allowing HIV escape. The signature residues Dr. West identified for these antibodies suggest a common pathway for developing potent CD4 binding site antibodies beginning with VH1-2-derived heavy chains, representing the likely way that these antibodies develop in humans, as evidenced by their independent isolation from five different individuals. Thus the increased understanding of critical features of recognition by this class of antibody is directly related to efforts to elicit these antibodies by vaccination.

March 2013

 

Alison Mahan

Ragon Institute of MGH, MIT and Harvard, US
Nominated by Dr. Julie McElrath

Alison Mahan is a graduate student in the lab of Dr. Galit Alter at the Ragon Institute of MGH, MIT and Harvard. She earned her undergraduate degree in biology at Reed College and is completing her PhD in Harvard University Program in Virology.

Alison’s work has focused on determining the mechanisms by which antibody glycosylation is programmed in B cells as part of the Ackerman/Alter CAVD project. Antibody glycosylation has been shown to be important both for determining the inflammatory profile of IgGs and modifying their capacity to induce effector functions, such as antibody dependent cellular cytotoxicity and phagocytosis. Her research focuses on the innate and adaptive signals that program specific changes in IgG glycosylation and seeks to determine which signals would be beneficial in the context of a vaccine to elicit highly functional HIV-specific antibodies. She has shown that activation of nucleic acid–sensing TLRs can induce significant changes in the expression of key glycosylation enzymes and is working to determine how the expression of these enzymes is regulated and programmed. Ultimately, understanding if and how antibody glycosylation is recalled will be important for eliciting antibodies with enhanced function through vaccination.

 

 

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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