Pathogens must preserve protein folding and function while experiencing environmental and host-derived stresses that can damage proteins and disrupt cellular homeostasis. Molecular chaperones and protein-quality-control systems are therefore essential components of pathogen survival.

We investigate Hsp70/DnaK chaperone systems and their co-chaperones, with particular interest in how nucleotide cycling, client recognition, and co-chaperone regulation influence protein folding and client fate.

Current questions include:

• How do pathogen Hsp70 systems differ in ATP/ADP cycling and nucleotide affinity?

• What molecular features determine which proteins or peptides are recognized as clients?

• How do DnaJ/Hsp40 proteins and nucleotide-exchange factors regulate Hsp70 activity?

• Do divergent pathogen chaperone systems employ distinct rules for protein folding, stabilization, and quality control?

By defining the biochemical and biophysical principles underlying pathogen proteostasis, we aim to identify mechanisms that distinguish these systems from their human counterparts and reveal potential vulnerabilities in infectious disease.

Maintaining balanced nucleotide pools is essential for DNA and RNA synthesis, energy metabolism, and cellular proliferation. We investigate enzymes that regulate nucleotide synthesis, interconversion, and energetic balance in medically important pathogens.

Current projects focus on kinases, phosphatases, and related metabolic enzymes from pathogens including Plasmodium sp, Neisseria gonorrhoeae, Chlamydia trachomatis, Trypanosoma sp, and other infectious organisms.

Using comparative enzymology, nucleotide-binding measurements, structural biology, and computational analysis, we seek to determine:

• how pathogen enzymes distinguish among closely related nucleotide substrates;

• how unique structural features regulate catalytic activity and substrate selectivity;

• how these enzymes contribute to nucleotide balance and pathogen survival; and

• whether pathogen-specific molecular features provide opportunities for selective therapeutic intervention.

A major focus is understanding how evolutionarily divergent nucleotide-processing enzymes have adapted to the specialized metabolic requirements of human pathogens.

A complementary area of the laboratory investigates the molecular basis of cardiovascular diseases that disproportionately affect underserved populations.

We integrate proteomics, genomics, bioinformatics, and molecular biology to identify pathways associated with disease development, progression, and recovery. Current interests include hypertensive heart disease and Chagas disease.

These studies seek to identify:

• molecular pathways associated with disease susceptibility and progression;

• protein and genomic signatures with potential biomarker value;

• mechanisms linking cellular stress and protein-quality-control pathways to cardiac dysfunction; and

• biological differences that may contribute to disparities in cardiovascular outcomes.