Research Focus Areas
Where collaborative science moves ideas from targets to therapies
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Biologics
The biologics focus area advances research on immune modulation, gene and mRNA therapies, and engineered proteins. Scientists in this area investigate immune regulation, cancer resistance mechanisms and therapeutic delivery at the cellular level. Their work bridges discovery and clinical translation, creating next-generation biologic agents to prevent, treat and cure disease.
Areas of Focus
- Cell-targeted gene therapy using AAV, lentivirus-like particles and nanoparticles
- CRISPR/Cas genome editing
- mRNA-based antibody, vaccine and cytokine replacement therapy
- HIV and NeuroHIV cure
- Neurodevelopmental and neurodegenerative diseases
- Gastrointestinal diseases
Select Projects
- T cell-targeted HIV cure: CD4-targeted delivery of compact Cas12f with multiplexed gRNAs for in vitro and in vivo studies, including humanized mouse and non-human primate models
- Microglia-targeted NeuroHIV cure: Development and screening of AAV serotypes and Exo-ERVLP approaches to cross the blood–brain barrier and edit provirus in microglia
- Exin21 mRNA booster: A 21-mer motif that stabilizes mRNA and enhances protein expression in vitro and in vivo for antibodies, vaccines and cytokines, with potential to improve efficacy and reduce manufacturing costs
Lab director: Wenhui Hu, Ph.D.
- Dissects how stress-sensing molecules, pattern recognition receptors and sentinel immune cells coordinate host defense
- Translates mechanistic insights into immune-modifying strategies for cancer and autoimmune disease
- Led a phase I clinical trial of a melanoma-targeted recombinant chaperone vaccine
- Engineers and tests immunostimulatory agents such as oncolytic viruses and antibodies to overcome barriers in the tumor microenvironment
Lab director: Xiang-Yang Wang, Ph.D.
- Develops therapeutic strategies to overcome drug resistance and identifies new cancer targets
- Discovered PEPD-G278D, a recombinant human protein that dual-degrades EGFR and HER2
- Demonstrated strong preclinical inhibition of tumors overexpressing EGFR, HER2 or their oncogenic mutants
- Advances PEPD-G278D toward clinical evaluation for cancers such as HER2-positive breast cancer and non-small cell lung cancer
Lab director: Yan Zhang, Ph.D.
Cancer
Research in cancer at the Center focuses on identifying new molecular targets and developing innovative therapeutics that enable personalized medicine and improve diagnosis, prevention and treatment outcomes. Projects span medicinal chemistry, molecular biology and immunology to translate discoveries into next-generation therapies.
- Designs heparin-mimicking compounds such as G2.2 that selectively inhibit cancer stem cell growth
- Investigates mechanisms involving p38 MAPK, IGF-1R and FGFR to block tumor proliferation in mice
Lab director: Umesh Desai, Ph.D.
- Develops irreversible inhibitors for AGC kinases using activity-based protein profiling
- Aims to identify and quantify activated kinase forms for improved cancer diagnosis
Lab director: Keith Ellis, Ph.D.
- Applies fragment-based discovery to design inhibitors for glutathione peroxidase 4
- Targets ferroptosis pathways in drug-resistant cancer cells
Lab director: Brian Fuglestad, Ph.D.
- Develops potent inhibitors (IC50 = 60 nM) targeting protein N-terminal methyltransferase 1
- Explores new approaches to personalized therapy for melanoma, colorectal and thyroid cancers
Lab director: Rong Huang, Ph.D.
- Uses fragment-based drug design to create small molecules that overcome taxol resistance
- Leads efforts to optimize NT-7-16, a microtubule destabilizer binding to the colchicine site of tubulin
Lab director: Glen Kellogg, Ph.D.
- Investigates transcriptional dysregulation in head and neck squamous cell carcinoma and colorectal cancer
- Combines biochemical, biophysical and animal models to study oncogenic transcription factors such as FOSL1, NF-κB and β-catenin
- Collaborates with structural biologists and medicinal chemists to develop PROTAC degraders and small-molecule inhibitors
Lab director: Jiong Li, Ph.D.
- Explores immune responses to oral bacteria and their role in periodontal disease and oral cancer
- Studies immune regulators including SGK1 and HDAC6 to restore immune balance
- Investigates how oral microbiota shape tumor microenvironments and contribute to chemoresistance
Lab director: Huizhi Wang, Ph.D.
Cognitive Disorders
Research in cognitive disorders explores the molecular mechanisms and structural biology underlying neurodegenerative diseases such as Alzheimer’s disease. Center scientists investigate how proteins, inflammation and cellular stress contribute to disease onset and progression, with the goal of identifying therapeutic targets and developing small molecules that restore or protect brain function.
- Determines high-resolution X-ray and cryo-EM structures of membrane proteins, including the translocator protein
- Applies structural insights to Alzheimer’s disease drug discovery
Lab director: Youzhong Guo, Ph.D.
- Examines interactions between amyloid-beta peptides and inflammatory proteins
- Studies how these interactions trigger reactive oxygen release from activated microglia
Lab director: H. Tonie Wright, Ph.D.
- Develops small-molecule therapeutics for neurodegenerative and inflammatory diseases
- Designs and optimizes compounds targeting mitochondrial complex I as neuroprotective agents
- Creates novel NLRP3 and GSDMD inhibitors as potential treatments for Alzheimer’s and related disorders
Lab director: Shijun Zhang, Ph.D.
Formulation
Research in formulation focuses on developing innovative aerosol and nasal drug delivery systems that improve treatment efficiency and expand therapeutic options. Center scientists explore how physical and chemical properties of formulations interact with device design to optimize drug delivery for respiratory and neurological conditions.
- Designs and evaluates novel aerosol drug delivery formulations targeting the lungs and nose
- Investigates effects of physical, chemical and formulation factors on aerosol performance
- Develops synthetic lung surfactant formulations for treating respiratory distress syndrome (RDS)
- Creates high-efficiency dry powder inhalers for antibiotics and antivirals, including medical countermeasures
- Explores nasal aerosol delivery for direct brain targeting in neurological disease treatment
- Collaborates with computational fluid dynamics and design engineering experts to optimize aerosol systems
Lab director: Michael Hindle, Ph.D.
Heart, Lung and Blood
Research in heart, lung and blood disorders aims to uncover molecular mechanisms that drive cardiovascular, pulmonary and hematologic diseases and to identify novel therapeutic strategies. Center investigators study how enzyme regulation, protein structure and redox biology influence disease progression and treatment response, with a focus on translating findings into clinically relevant therapies.
- Studies the structural and mechanistic basis of macromolecular complexes involved in protein folding and degradation
- Explores how chaperone-mediated protein quality control impacts cardiac and pulmonary disease
Lab director: Qinglian Liu, Ph.D.
- Designs small molecules to stabilize or modulate hemoglobin for treating sickle cell disease and other blood disorders
- Uses structure-based drug design to develop enzyme inhibitors that regulate redox balance and oxidative stress
- Investigates the relationship between protein conformational changes and disease-related dysfunction
Lab director: Martin Safo, Ph.D.
Imaging and Diagnostic Agents
Research in imaging and diagnostic agents focuses on developing molecular probes and radiotracers that enhance early disease detection and guide therapeutic decisions. Scientists apply molecular imaging, medicinal chemistry, and radiochemistry to design tools that visualize disease processes and evaluate treatment efficacy.
- Develops positron emission tomography (PET) radiotracers targeting NLRP3, GSDMD and complex I
- Uses these biomarkers to improve drug discovery and preclinical evaluation
- Explores novel chemical scaffolds for molecular imaging and diagnostic applications
Lab director: Shijun Zhang, Ph.D.
Infectious Diseases
Research in infectious diseases develops next-generation strategies to prevent and treat infection as pathogens evolve resistance to existing drugs. Projects span vaccine design, host–pathogen interactions and small molecules that disable bacterial virulence or viral replication.
- Develops PHE as an anti-influenza agent that disrupts the M1 layer and inhibits multiple viral strains including H1N1, H3N2 and H5N1
- Collaborates with Martin Safo to define mechanisms and optimize efficacy
Lab director: Umesh Desai, Ph.D.
- Determines and models the cytomegalovirus nuclease structure to understand replication and enable structure-based antiviral design
- Collaborates with Martin Safo and clinical partners to advance leads
Lab director: Glen Kellogg, Ph.D.
- Studies genetics, physiology and host–pathogen interactions of Borrelia burgdorferi, Treponema denticola and Porphyromonas gingivalis
- Combines genetics, biochemistry, biophysics, cell biology and animal models to define mechanisms of pathogenesis
Lab director: Chunhao Li, Ph.D.
- Designs small molecules that inhibit the Type III Secretion System to block Gram-negative pathogen infection
- Identifies inhibitors of the Type IV Secretion System to limit conjugative transfer of antibiotic resistance genes
Lab director: Aaron May, Ph.D.
- Engineers hepadnaviral core proteins that present malaria B cell and T cell epitopes in highly immunogenic vaccine candidates
- Leads structural studies of a Staphylococcus aureus protease essential for ribosomal maturation and viability to enable inhibitor design
Lab director: Darrell Peterson, Ph.D.
- Collaborates on anti-influenza strategies that target M1 oligomerization and block viral assembly
- Determines viral enzyme structures to guide antiviral discovery
Lab director: Martin Safo, Ph.D.
- Designs drug formulations that enable controlled nitric oxide release from implant surfaces to prevent device-associated infection
- Targets both planktonic and biofilm bacteria on catheters, cannulas and sensors
Lab director: Xuewei Wang, Ph.D.
Molecular Design Algorithms
The molecular design algorithms focus area develops computational tools and mathematical models to accelerate drug discovery and protein engineering. Researchers integrate quantum chemistry, applied mathematics and machine learning to better predict molecular behavior and design targeted therapeutics.
- Develops algorithms that detect and exploit three-dimensional hydropathic interaction homologies within protein structures to improve prediction accuracy
- Creates computational methods to identify small-molecule inhibitors of protein–protein interactions, incorporating water dynamics and local pH effects
Lab director: Glen Kellogg, Ph.D.
- Integrates applied mathematics and machine learning with electronic structure theory to accelerate quantum chemistry calculations while preserving accuracy
- Uses Grassmannian geometry to enhance chemical discovery and guide the rational design of light-responsive molecular devices
- Applies set theory-based fragmentation to enable efficient reaction and interaction energy calculations for complex biological systems
- Builds data-driven quantum chemistry models that scale to large systems and improve predictions of molecular properties
Lab director: Ka Un Lao, Ph.D.
Substance Use Disorders
Research in substance use disorders aims to develop safer and more effective therapeutics for addiction and overdose. Investigators focus on the pharmacology of opioid receptors, design of novel modulators, and discovery of compounds that address treatment-resistant psychiatric and neurological conditions.
- Investigates existing and novel compounds for treating neuropsychiatric disorders, pain and substance abuse
- Uses synthesis, computational modeling and pharmacological assays to study mechanisms of action
- Explores serotonergic psychedelics for treatment-resistant depression
- Develops monoamine transporter reuptake inhibitors and organic cation transporter agents as new therapeutic approaches
Lab director: Malgorzata Dukat, Ph.D.
- Designs novel mu-opioid receptor modulators to counteract synthetic opioids such as fentanyl and nitazene derivatives
- Combines computational modeling, chemical synthesis and biological testing to create safer treatments for opioid use disorder and overdose
- Develops MOR-selective bitopic ligands that engage both orthosteric and allosteric sites to refine receptor targeting
Lab director: Piyusha Pagare, Ph.D.
- Designs and evaluates mu-opioid receptor modulators to treat opioid addiction
- Develops fentanyl-specific counteracting agents for overdose treatment
Lab director: Yan Zhang, Ph.D.