Research Areas


Blood and cardiovascular diseases are the underling cause of ~50% of all disease-related deaths in the US. ISB3D researchers have developed several promising compounds as anticoagulants and antisickling agents. The following are some highlights.

  • Four molecules (SPGG, SCI, SMI and SG-09) identified as preventing thrombosis at 25 – 250 g per mouse (1.25–12.5 mg/kg) dose as selective (>200-fold selectivity) factor XIa targeting anticoagulants through an allosteric inhibition mechanism ... Umesh Desai
  • Allosteric modifiers of hemoglobin with nitric oxide releasing ability, which can increase both erythrocyte mobility and tissue oxygen and have potential application in stroke, myocardial infraction, and vasoconstriction prevention ... Martin Safo
  • Structure-function studies of hemoglobin and rational design of antisickling agents to treat sickle cell disease; Two drugs have been developed, one currently in phase II clinical study, and the other preclinical study ...  Martin Safo

Cancer continues to be challenging to public health, with nearly 2,000 deaths and 5,000 new cases per day. ISB3D researchers focus on the discovery of new anti-cancer targets as personalized medicine and new approaches for the diagnosis, prevention, and treatment of cancer.  The following are some highlights.

  • Potent inhibitors (IC50 = 60 nM) have been developed to specifically target protein N-terminal methyltransferase 1, which represents a potential new approach to personalized cancer therapy including melanoma, colorectal and thyroid cancer ... Rong Huang
  • G2.2 and its analogs structurally mimic heparin hexasaccharide; selectively inhibit cancer stem cells growth and self-renewal in colorectal, pancreatic and breast cells through activation of p38 MAPK involving IGF-1R and FGFR; G2.2 inhibits CSCs proliferation in mice xenografts ... Umesh Desai
  • Irreversible inhibitors for the AGC kinase as an activity-based protein profiling to selectively identify and quantify the activated form in cells for detection and diagnosis ... Keith Ellis
  • A small molecule called NT-7-16 has been identified as a microtubule destabilizer (30 nM potency) and anti-proliferation agent (10 nM potency) by binding in tubulin’s colchicine binding site; indications are that it overcomes taxol resistance. ISB3D researchers are leading the drug design efforts to discover even more efficacious agents ... Glen Kellogg

Cognitive disorders become an increasingly important public health problem. ISB3D researchers are working on new mechanism and therapeutic approaches to diseases like Alzheimer’s disease. The following are some highlights.

  • Interactions of the Alzheimer’s amyloid peptide Aβ in its different forms with inflammatory proteins and the effects of these interactions on reactive oxygen release from activated rodent microglia ... H. Tonie Wright
  • High-resolution X-ray crystallographic and cryo-electron microscopic structures of membrane proteins like the translocator protein for Alzheimer’s Disease drug discovery and development ... Youzhong Guo 

Infectious diseases pose a great threat to human health. Pathogens continually evolve to anti-infectious agents, making future generations more difficult to treat. This requires the continued development of new strategies to fight and prevent infection.   

  • Development of a recombinant hepadnaviral core protein engineered to present malaria B cell and T cell epitopes in a highly immunogenic form that can function as a vaccine to elicit protective antibodies in recipients ... Darrell Peterson
  • PHE as an anti-influenza agent that disrupts the M1 layer; it inhibits M1 oligomerization at 1-5 M and inhibits multiple viral strains including H1N1, H3N2, and H5N1 ... Umesh Desai and Martin Safo
  • Many Gram-negative pathogenic bacteria, such as enteropathogenic E. coli, Salmonella enterica serotype Typhi and Yersinia pestis, use a conserved virulence apparatus called the Type III Secretion System (TTSS) to infect eukaryotic host cells. The synthesis of new and more potent TTSS inhibitors that function by preventing pathogenic bacteria from using their TTSS to cause infection is being pursued at the ISB3D, as well as studies to more precisely define their molecular targets ... Aaron May
  • Conjugation is a process used by many Gram-negative and Gram-positive bacteria to share antibiotic resistance genes, even if they have not been previously exposed to a specific drug.  This process is enabled by an apparatus called the Type IV Secretion System (T4SS), and inhibiting T4SS is a next-generation strategy to limit antibiotic resistance gene transfer ... Aaron May
  • Structural studies of a S. aureus protease essential for ribosomal maturation and bacterial viability is being investigated as a basis for inhibitor design and screening ... Darrell Peterson, J. Neel Scarsdale, H. Tonie Wright in collaboration with Gail Christie in the Dept. of Microbiology, School of Medicine
  • Human cytomegalovirus (CMV) is a significant human pathogen with a need for safer and more effective therapeutics. ISB3D members are determining the crystal structure of the viral nuclease, which will form a basis for understanding the biochemical activities of the nuclease, its role in viral replication, and for exploiting the nuclease as a target for anti-viral drug discovery ... Martin Safo, Glen Kellogg in collaboration with Michael McVoy in the Dept. of Pediatrics, School of Medicine
  • The majority of chronic tobacco smokers develop emphematous lung, resulting in chronic obstructive pulmonary diseases (COPDs). No treatment is available to date that cures emphematous lung and all current treatments provide only symptomatic relief. Researchers at the ISB3D have developed novel molecules that not only prevent but cure emphysema/COPD ... Umesh Desai in collaboration with Masahiro Sakagami in the Dept. of Pharmaceutics, School of Pharmacy
  • Development of new and novel algorithms that are based on detecting and exploiting the underlying three-dimensional hydropathic interaction homologies within protein structure, which is a new strategy for protein structure prediction ... Glen Kellogg and J. Neel Scarsdale
  • One of the evolving strategies for drug discovery is targeted inhibition of protein-protein interactions by small molecules.  Unfortunately, the results to date have been unimpressive, and new approaches are necessary.  ISB3D researchers are exploring new theories and methods that exploit water, local pH and the hydrophobic effect ... Glen Kellogg, J. Neel Scarsdale in collaboration with Peter Uetz in the Center for the Study of Biological Complexity, Life Sciences
  • New synthetic routes for peptide-SAM conjugates developed in Huang lab can be easily adapted to develop potent and selective inhibitors for any protein methyltransferase ... Rong Huang