Research Programs

The Institute’s current group of Fellows and their research initiatives includes:

Dr. John Siekierka (Director & Chemistry and Biochemistry) and Dr. Ronald Goldberg (Associate Fellow): Inhibitors of parasitic mitogen-activated protein kinases (MAPKs) as potential anti-parasitic therapeutics and the mechanism of HIV Nef protein activation of host p38 MAPK and induction of Fas ligand.

We are focused on the development of small molecule inhibitors of parasite mitogen-activated protein kinases (MAP kinases) as potential therapeutic agents. Research is currently underway on a Leishmania MAPK and a MAPK found in the parasitic nematode, Brugia malayi. Leishmania, the causative agent of Leishmaniasis, is second only to malaria in terms of global morbidity. Brugia malayi is the causative agent of Lymphatic filariasis or elephantiasis, a serious debilitating disease endemic in Southeast Asia and Indonesia. Our laboratory also conducts research on HIV viral protein interactions with host p38 MAP kinase leading to evasion of virally-infected T-cell from immune surveillance.

Dr. Ronald Goldberg has joined Dr. Siekierka’s laboratory as Associate Sokol Institute Fellow. Dr. Goldberg has over 20 years of experience in pharmaceutical research and most recently was laboratory director at Novartis. Dr. Goldberg’s expertise is in Inflammatory Diseases, assay development and high-throughput screening.

Dr. Nina Goodey (Chemistry and Biochemistry) and Dr. Katherine Herbert (Computer Science): “Predicting drug-target relationships for dihydrofolate reductase (DHFR) homologs through phylogenetic analysis”.

The goal of this project is to discover and exploit homology relationships between DHFRs from various organisms and to predict novel drug-DHFR interactions in pathogenic organisms through the creation of a new computational toolkit called “DrugTree”. We are using the enzyme dihydrofolate reductase as a model system to predict which existing drugs that have already been found to successfully inhibit this enzyme in one organism can be used to inhibit the same enzyme in another organism, thereby leading to new therapeutic uses for know drugs. While these tools will be applicable to other enzyme systems, dihydrofolate reductase is both an important target and a good model system. This enzyme is a validated drug target for treatment of various parasitic diseases such as malaria, trypanosomiasis (African sleeping sickness), Changa’s disease, and tuberculosis.

Dr. Hans Schelvis (Chemistry and Biochemistry) and Dr. Carlos Molina (Biology and Molecular Biology): “Binding of ICER (Inducible cAMP Early Repressor ) to Its Own Promoter as a Mode of Cooperative Regulation”.

Inducible cAMP Early Repressor (ICER) is a regulator of cAMP signaling in the cell. ICER can be found in normal cells but it is not present in tumor cells. The growth of these tumor cells is attentuated when ICER protein is artificially reintroduced in these cells. Therefore it is hypothesized that ICER manipulation could potentially be used as a new therapy for the treatment of cancer. Although much is known about the physiological role of ICER, little is known about the regulation of the gene. We are studying one aspect of ICER regulation, negative autoregulation of ICER by binding to its own regulatory sequences. In other words, how the ICER protein can turn off its own production in the cell, when its concentration in the cell becomes too high.