Pilot Projects

The COBRE Pilot Grant Program

The University of Kentucky Center for Molecular Medicine will make available pilot research grants. These pilot grants are intended to fund:

  • tenure track early career junior faculty (Assistant Professor level) 
  • established tenure track faculty developing a new research area (all tenure track ranks) and
  • tenure track faculty developing a Multi-PI or Program Project Grant (all tenure track ranks).

Research projects should fit into the general theme of the molecular basis of human disease. These pilot grants are intended to provide funding to enable the recipient to generate sufficient data to apply for extramural funding. They are awarded in the amount of up to $50,000 per year for two years.  

Who is Eligible to Receive a COBRE Pilot Grant?

Tenure track faculty at the University of Kentucky.  Applicants applying for an early career junior faculty pilot grants cannot have or have had an RO1 type NIH grant or the equivalent NSF grant. Individuals who have or have had other types of grants such as NIH K or R21 awards or association or foundation awards are eligible. 

Application Form

Applications are currently not being accepted.

Current Pilot Projects

The following pilot projects are currently being funded for the 2017 grant year:

Principal Investigator:  Dr. Craig Vander Kooi

Department of Molecular and Cellular Biochemistry

Title:  Function of GIPC3 in hearing loss

Abstract:  The GIPC family of proteins function as key molecular scaffolds that are critical in the physical integration of multiple steps of signaling from receptor activation to intracellular signaling. GIPC3 plays an essential role in the auditory system, with mutations in GIPC3 causing inherited nonsyndromic hearing loss. Despite this unique and crucial function in the auditory system, the molecular function and why mutations in the GIPC3 gene leads
to hearing loss, is unknown. We will define the structural basis for GIPC3 function, and the mechanism(s) by which the eleven reported patient mutations lead to inherited hearing loss. Defining the structure and functional interactions of GIPC3, and the molecular basis for dysfunction, requires an integrated structural, biochemical, and physiological approach that form the heart of our proposed work. In Aim 1, we will determine the basis for GIPC3 coupling to the NMDA glutamate receptor. Aim 2 will focus on conformational dynamics associated with activation of GIPC3, and how this leads to engagement of the Myo6 motor protein. Taken together, these studies contribute to our long-term goal of understanding the physical mechanisms underlying the role GIPC3
in normal physiological function, and will inform ongoing efforts to understand and ameliorate GIPC3 dysfunction in disease.

Principal Investigator:  Dr. Adam Bachstetter

Spinal Cord & Brain Injury Research Center

Title:  Role of MK2 following traumatic brain injury

Abstract:  This 2-year pilot award will generate preliminary data investigating the role of MAPK-activated protein kinase 2 (MK2) following traumatic brain injury (TBI). Despite multiple attempts no drug has earned FDA approval for TBI. Control of neuroinflammation is a promising avenue to achieve neuroprotection and improve patient outcomes. Still, there is an urgent need to identify the molecular mechanisms that regulate inflammation, so
selective therapeutic agents can be developed. Our prior work has demonstrated that the mitogen-activated protein kinases (MAPK) pathway is involved in detrimental neuroinflammation following injury or in neurodegenerative disease [1-4]. From our prior work we have recently identified the protein MK2, which we postulate maybe an enzyme specific to the detrimental proinflammatory response to TBI. Using a mild closed head injury model in mice we will address our overall hypothesis: MK2 deficiency will prevent TBI induced neurological deficits. If successful, we will have identified a novel therapeutic target that regulates neuroinflammation following TBI, which will lay the foundation to garner NIH funding to explore the pathway in greater detail.

Principal Investigator:  Dr. Jessica Blackburn

Department of Molecular and Cellular Biochemistry

Title:  Single Cell Characterization of Leukemia Stem Cells

Abstract:  Patients with relapsed Acute Lymphoblastic Leukemia (ALL) have a poor prognosis because their therapeutic options are limited. Relapse is thought to arise from leukemia stem cells, which have the unique ability to self-renew to reform tumor from a single cell. These cells are rare in human
disease and mouse models, making up <0.0001% of the total leukemic cell population. Because we do not yet know how to reliably isolate these cells from the bulk of the tumor, leukemia stem cells are not well characterized, despite their importance in ALL progression and relapse. We have developed a
zebrafish model of ALL in which leukemia stem cells make up ~10% of the tumor cell population. The goals of this proposal are to characterize leukemia stem cells from T-ALL functionally through single cell transplantation, and genetically through single cell RNA sequencing. With this preliminary data, we
will apply for R01 funding from NCI to scale up single cell sequencing efforts, and to use zebrafish ALL models for in vivo drug screens to identify compounds that target leukemia stem cells. These data will ultimately provide new and important insights into cancer biology and will lead to the identification of
new targets for anti-cancer therapies.

Principal Investigator:  Dr. Anthony Sinai

Principal Investigator:  Dr. Matthew Gentry

Department of Microbiology, Immunology, and Molecular Genetics/ Department of Molecular and Cellular Biochemistry

Title:  Carbohydrate Metabolism as a drug target against Toxoplasma gondii cysts

Abstract:  Active infection by Toxoplasma gondii, triggers an immune response that promotes conversion of the fast growing tachyzoite into the slow growing bradyzoites that reside within tissue cysts. The absence of drugs that target bradyzoites or prevent their transition to active growth stems from our limited understanding of tissue cyst biology. The Sinai laboratory has developed methodologies that permit for the first time the rigorous addressing of tissue cyst biology. A morphological feature of bradyzoites within tissue cysts is the presence of amylopectin granules (AGs). AGs are analogous to glycogen and starch, but are more similar to insoluble starch. Our data, indicating active replication and mitochondrial respiration in bradyzoites suggest the AGs may be critical in the maintenance of bradyzoite viability-in addition to powering reactivation. The identification of Toxoplasma homologs of the carbohydrate phosphatase Laforin (TgLaforin) and Glucan water dikinase (GWD) reveal the essential elements in AG metabolism in the parasite. The Gentry laboratory has cloned TgLaforin, and has extensive experience working with GWD. This can be applied immediately to Toxoplasma.  With this collaborative project we aim to establish the potential of carbohydrate metabolism as a cyst specific drug target which would lay the foundation for major funding from the NIH.

Principal Investigator:  Dr. David Rodgers

Department of Molecular and Cellular Biochemistry

Title:  Polyanions in localization and activity of insulin degrading ensyme

Abstract:  The zinc metallopeptidase insulin degrading enzyme (IDE, insulysin) is primarily responsible for insulin catabolism and plays a key role in Alzheimer’s disease as one of a few enzymes that degrade amyloid beta peptide. Effective modulators of IDE activity would therefore be useful in treating human diseases. The goal of this study is to understand the role of inositol phospholipids and inositol phosphates in localizing and
activating IDE in cells. We propose that binding phosphatidyl inositol phosphates localizes IDE to endosomes, contributing to insulin degradation and secretion of IDE, and that inositol phosphates activate IDE toward cytosolic substrates. We will use cell-based assays to test this proposal. Three specific aims are proposed: 1) to determine if IDE binding phosphatidyl inositol phosphates is important in localization to endosomes and intracellular insulin catabolism; 2) to determine if inositol phosphates participate in the trafficking of IDE to the plasma membrane and the secretion of IDE from cells; and 3) to determine if the intracellular degradation of amyloid precursor protein intracellular domain (AICD) by IDE is regulated by inositol phosphates. This work will address important questions regarding IDE regulation and lay the foundation for developing modulators of IDE activity that can be used clinically.

Principal Investigator:  Dr. Jose Abisambra

Sanders-Brown Center on Aging

Title:  PERK inhibition for traumatic brain injury therapy

Abstract:  Traumatic brain injury (TBI) is a leading cause of death, disability, and mental handicap. Currently, ~1.7 million people in the US sustain a head injury annually. An unexplained feature of TBI patients is onset of cognitive dysfunction years after injury. Despite promising preventative strategies, there are currently no effective therapeutic interventions after TBI. This is partly because the molecular mechanisms linking head trauma and neuronal dysfunction are still unknown.  We recently identified that an early feature of TBI is sustained activation of the endoplasmic reticulum (ER) stress sensor PERK, Protein Kinase R-like ER Kinase. Normally, when a cell is subjected to ER stress, activation of PERK temporarily inhibits protein synthesis thereby restoring ER homeostasis. However, long-term PERK activity mediates neuronal dysfunction due to this decrease in translation. We hypothesize that TBI chronically induces PERK activation debilitating neuronal function which contributes to cognitive decline. We will test this hypothesis by first determining the mechanisms by which TBI drives PERK, and then we will restore brain function by inhibiting PERK after injury (Fig. 1). Successful completion of these aims will highlight PERK as a novel therapeutic target for TBI.