The 2009 Postdoctoral Fellow Research Poster Competition

Highlighting areas of research that range from malaria to arterial disease, the Postdoctoral Fellows’ Research Poster Session was held April 16–17, 2009, in Feinstone Hall. This event, sponsored by the Office of Graduate Education and Research, was organized to spotlight the research of our postdoctoral fellows. Twenty postdoctoral fellows participated in the event.

On April 17, a panel of four faculty judges chose first- and second-place winners in two categories:

• Laboratory-based research
• Epidemiological/social/behavioral research

Janet DiPietro, associate dean of research, presented the awards. First-place prizewinners received $1,500 each, and the runners-up received awards of $1,000.

LABORATORY-BASED RESEARCH

First place
Debabani Roy Chowdhury
Molecular Microbiology & Immunology
Mentor: Nirbhay Kumar
A potent transmission-blocking vaccine based on codon-harmonized Pfs48/45 [abstract]

Second place
Sung-Jae Cha
Molecular Microbiology & Immunology
Mentor: Marcelo Jacobs-Lorena
Molecular mechanisms of mammalian liver invasion by the malaria parasite

EPIDEMIOLOGICAL/SOCIAL/BEHAVIORAL RESEARCH

First place
Jared Reis
Epidemiology
Mentor:  Edgar (Pete) Miller
Low vitamin D contributes to the racial disparity in peripheral arterial disease among U.S. black adults [abstract]

Second place
David Lopez
Epidemiology
Mentor: Elizabeth Platz
Racial/ethnic differences in the association of body composition and fat distribution with circulating hormones in U.S. men

ABSTRACTS

Debabani Roy Chowdhury

A potent transmission-blocking vaccine based on codon-harmonized Pfs48/45
Malaria caused by Plasmodium falciparum is responsible for nearly 1 million deaths annually. Although much progress has been made in the recent past, the development of a safe, effective and affordable malaria vaccine has remained a challenge. The various vaccines under development include those targeting pre-erythrocytic stage of the parasite to prevent infection, erythrocytic stages to reduce clinical severity and sexual stages to reduce and/or stop malaria transmission. A vaccine targeting sexual stages will not only reduce malaria transmission by female anopeline mosquitoes, but also reduce spread of parasites becoming non-responsive to vaccines targeting pre-erythrocytic and erythrocytic asexual stages. Towards this end, we focused our studies on Pfs48/45, a protein expressed in the sexual stages developing within an infected person and one of the most promising transmissionblocking vaccine targets. Functional immunogenicity of Pfs48/45 protein requires proper disulfide bond formation, consequently evaluation of immunogenicity of recombinant form of full length Pfs48/45 has been hampered by difficulties in expressing properly folded protein to date. Here we present a strategy involving harmonization of the codons for successful recombinant expression of full length Pfs48/45 in Escherichia coli. The purified protein, designated CH-rPfs48/45, was recognized by monoclonal antibodies directed against reduction-sensitive conformational epitopes in the native protein. Immunogenicity evaluation in mice revealed potent transmission blocking activity in membrane feeding assays of antisera elicited by CH-rPfs48/45 formulated in three different adjuvants, i.e. Alum, Montanide ISA-51 and complete Freund’s adjuvant. More importantly, CH-rPfs48/45 formulated with Montanide ISA-51 when administered to nonhuman primates (Olive baboons, Papio anubis) resulted in uniformly high antibody responses (ELISA titers > 2 million) in all five animals, which in membrane feeding assays displayed greater than 93% blocking activity after a single immunization reaching nearly complete blocking after a booster dose of the vaccine. The relative ease of expression and induction of potent transmission blocking antibodies in mice and nonhuman primates provide the compelling rationale and basis for development of a CH-rPfs48/45 based malaria transmission blocking vaccine.

Jared Reis

Low vitamin D contributes to the racial disparity in peripheral arterial disease among U.S. black adults

Background: Racial differences in established cardiovascular risk factors do not completely explain the higher frequency of lower-extremity peripheral arterial disease (PAD) experienced by black adults. Low vitamin D status, which is highly prevalent among black adults due in part to increased skin pigmentation, has emerged as a novel cardiovascular risk factor. However, it is unknown whether low vitamin D levels contribute to the excess risk for PAD experienced by black adults.

Objective: We sought to determine whether any of the excess risk for PAD among black adults may be explained by racial differences in vitamin D status.

Methods: This population-based cross-sectional study included 2,987 white and 866 black US adults >40 years from the 2001-2004 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial pressure index <0.90 in either leg.

Results: Mean (±SEM) serum 25-hydroxyvitamin D [25(OH)D] levels were lower in black compared to white adults (39.2±1.0 vs. 63.7±1.1 nmol/L, respectively, p<0.001). Adjusted odds ratios for PAD decreased in a dose-dependent fashion with increasing quartile of 25(OH)D in white adults [1.00 (referent), 0.86, 0.67, 0.53; ptrend<0.001]. In black adults, the association was non-linear; models with cubic splines suggested a higher prevalence of PAD at the lowest and a lower prevalence at the highest concentrations of 25(OH)D. After accounting for racial differences in socioeconomic status as well as traditional and novel risk factors, the odds ratio for PAD in black adults was reduced from 2.11 (95% CI: 1.55, 2.87) to 1.67 (95% CI: 1.11, 2.51). Following additional adjustment for 25(OH)D, this odds ratio was further reduced to 1.33 (95% CI: 0.84, 2.10).

Conclusions: Low vitamin D levels may explain nearly one-third of the excess risk for PAD experienced by black adults. Improving vitamin D status may be a simple and cost-effective means for reducing the excess burden of PAD among black adults in the US.