Research Projects

Defining and Characterizing Drivers of Lethal Metastatic Prostate Cancer, lead by Grinu Mathew, PhD, assistant professor, UNMC Eppley Institute for Research in Cancer and Allied Diseases.

Goals:

1. Define the role of Axl kinase receptor in PC metastasis.
2. Dissect the effect of androgen deprivation therapy on Pten/Trp53/Axl-null cells.
3. Investigate the cell intrinsic signaling dependencies of Axl-deficient cells.

Differential Cell Size in Epithelial Packing, Homeostasis, and Disease, lead by Subramanian Ramanathan, PhD, assistant professor, UNMC Department of Genetics, Cell Biology and Anatomy.

Goals:

1. Determine how the Lgr5+ stem cells and Paneth cells of the small intestine maintain a checkerboard-like architecture.
2. Interrogate how aberrant changes in nuclear and cellular size are accommodated in the villi.

Targeting ASAP1-Controlled Signal Pathways to Inhibit Uveal Melanoma Metastasis, lead by Jae Hyuk Yoo, PhD, assistant professor, UNMC Department of Ophthalmology and Visual Sciences.

Goals:

1. Identify ASAP1 domain(s) that promote uveal melanoma cell invasion and proliferation.
2. Assess the function of ASAP1-controlled transcription factor(s) in uveal melanoma cell invasion, proliferation, and tumor metastasis in a xenograft model of human uveal melanoma.

Novel Mechanisms of Inhibiting Transcriptional Coactivators for Anti-Cancer Therapy in Colorectal Cancer, lead by Kurt Fisher, MD, PhD, assistant professor, UNMC Department of Pathology, Microbiology, and Immunology.

Goals:

1. Determine vulnerabilities within the HCF2 axis of PGC-1β-dependent transcription.
2. Validate that PGC-1β and HCF2 are therapeutic targets for metastatic CRC.

Development of Biodegradable Nanocarrier for Improved Co-delivery of PARPi and DNMTi, led by Jingjing Sun, PhD, assistant professor, UNMC College of Pharmacy Department of Pharmaceutical Sciences.

Goals:

1. Develop biodegradable bPAZA nanocarriers and evaluate the impact of polymer structure on the protein corona composition.
2. Develop a bPAZA polymer conjugated with cetuximab for improved tumor targeting.

Spartan Protease Repairs DNA-Protein Cross-Links and Prevents DPC-Induced Oncogenesis, lead by Gargi Ghosal, PhD, assistant professor, UNMC Department of Genetics, Cell Biology and Anatomy.

Goals:

1. Determine the molecular mechanism of SPRTN mediated DPC repair.
2. Examine the tumor suppressor function of SPRTN in hepatocellular carcinoma and target SPRTN protease activity for cancer therapy.
3. Determine the in vivo physiological function of SPRTN in segmental progeria and early-onset tumorigenesis.

Hematopoietic Signaling Pathway Mechanism in a GATA Factor-Dependent Network, lead by Kyle Hewitt, PhD, assistant professor, UNMC Department of Genetics, Cell Biology and Anatomy.

Goals:

1. To delineate the mechanism of Samd14 regulation of myeloid and erythroid progenitors.
2. To dissect mechanisms mediating anemia-dependent upregulation and hematopoietic function of the GATA-2-occupied Samd11 gene.
3. To establish Samd14 and Samd14-Enh function in hematopoiesis and myelopoiesis.

Role of E3 Ligase, UBR5, in Hematopoietic Differentiation and Lymphomagenesis, lead by Shannon Buckley, PhD, assistant professor, UNMC Department of Genetics, Cell Biology and Anatomy.

Goals:

1. To understand the role of Ubr5 in B-lymphoid lineage specification and identify small molecule inhibitors targeting mutant UBR5.
2. To determine the in vivo role of Ubr5 mutations in disease initiation and/or progression.
3. Identification of interacting partners and substrates of UBR5.

CTDP1 Regulates FANCI and the Response to DNA Interstrand Crosslinks, lead by Nicholas Woods, PhD, assistant professor, UNMC Eppley Institute for Research in Cancer and Allied Diseases.

Goals:

1. To characterize the impact of CTDP1-mediated FANCI phosphorylations on FA pathway response to ICL.
2. To characterize the impact of CTDP1 inhibition on ICL sensitivity in an orthotopic model of breast cancer.
3. To identify small molecule inhibitors of CTDP1 using high-throughput screening.

Activators of ClpP2 as New Antichlamydial Agents, lead by Martin Conda Sheridan, PhD, assistant professor, UNMC Department of Pharmaceutical Sciences.

Goals:

1. To design, synthesize, and optimize the molecular pharmacophore. Prepare a library of molecules. Purification. Characterization. Calculate properties in silico.
2. To evaluate the antibacterial and enzymatic activity. Inhibition of chlamydial growth. Toxicity towards host and against a panel of human cell lines. Test action against other bacteria to check selectivity. Mechanistic studies (degradation of casein) using recombinant ClpP proteins. Binding of selected molecules to ClpP2 using ITC.
3. To evaluate PK/PD properties and assess in vivo activity. Study the stability of selected molecules in human microsomes and hepatocytes. Evaluate key properties in vitro: stability in serum and simulated gastric fluid, absorption and efflux, blood/plasma partitioning, plasma protein binding, and solubility. Study biodistribution and efficacy in vivo.

Novel Mechanisms of Nuclear Phosphoinositide Signaling in Regulation of the YAP/TAZ Pathway in Triple-Negative Breast Cancer, lead by Suyong Choi, PhD, assistant professor, UNMC Eppley Institute for Research in Cancer and Allied Diseases. 

Goals:

1. Elucidation of the molecular interactions between PIPKIα, IPMK, and PI species with YAP/TAZ and TEADs.
2. Investigation of biological functions of nuclear PI-mediated YAP/TAZ regulation.

Mechanisms of Lipid Heterogeneity in Lipid Droplet Catabolism, lead by Micah Schott, PhD, assistant professor, UNMC Department of Biochemistry and Molecular Biology.

Goals:

1. Define the impact of lipolysis-generated diacylglycerol on lipid droplets.
2. Determine the impact of LD phosphoinositide dynamics on LD trafficking.