Instruction

Basic Research

BRCA1 functions as a breast/ovarian tumor suppressor by promoting high fidelity DNA repair and maintaining genome stability. While germline mutations of BRCA1 account for approximately 50% of familial breast cancer cases, somatic mutations of the gene are rarely found in sporadic breast cancer. Rather, a large number of invasive sporadic breast tumors express wild-type BRCA1 protein at relatively low levels, raising the possibility that BRCA1 may also contribute to sporadic breast cancer development and progression.

Induced pluripotent stem cells (iPS cells) have properties similar to those of embryonic stem cells, but they can be derived from any type of somatic cell, such as a skin fibroblast. iPS cells can provide access to specialized cells, such as neurons, in species that otherwise would be unavailable for biomedical research. Among nonhuman primates, the chimpanzee occupies a unique position for comparative biology. Here we propose to use iPS cells from three primates: the chimpanzee, marmoset, and human.

Myelodysplastic syndrome (MDS) is a group of disorders characterized by dysfunctional blood cells that can progress to acute myeloid leukemia (AML). At this time the etiology of MDS development and progression to AML is not understood and there is no cure (median survival at time of diagnosis is less than 5 years). Yet, DNA damage and mutations appear to play a key role with the initiating defect in a hematopoietic stem cell (HSC). In support, people with certain DNA repair defective syndromes including Fanconi anemia (FA) and Bloom syndrome (BS) exhibit MDS.

The groundbreaking discovery that adult cells can be reprogrammed into embryonic-like induced pluripotent stem (iPS) cells has developed excitement for future innovative patient-specific cell and tissue regeneration therapies. iPS cells can develop into any desired cell type under appropriate conditions. For regenerative dentistry goals, deriving cranial neural crest (CNC) cells from iPS cells is an important step for future development of iPS-derived cranial-facial structure regeneration therapies.

This is a multicenter, prospective, parallel, double-blinded, validation study of up to 12 weeks duration to evaluate the safety and effectiveness of CDO for the treatment of Diabetic Foot Ulcers at over 30 centers in the United States. The primary objectives of this study are: 1) to evaluate the effectiveness of CDO in combination with standard MWT on wound healing as compared to standard MWT alone; and 2) screening for potential safety issues.

The applicant's career goal is to become a surgeon-scientist studying translational research in regenerative medicine. A comprehensive mentoring plan with a team of mentors of diverse backgrounds will ensure the applicant's career development. The proposed studies will address the role of microRNAs (miRNAs) on the regulation of macrophage polarization in vitro and in the dynamic tissue events during skeletal muscle injury, macrophage recruitment, angiogenesis, and muscle regeneration.

Schizophrenia is a devastating psychiatric condition that affects up to 1% of the US population. During the previous funding period, we reported that a loss of hippocampal interneuron function, recapitulates the hyperdopaminergic state thought to underlie psychosis in patients. In addition, we have recently provided one of the first reports describing the feasibility of interneuron transplants (derived from fetal medial ganglionic eminence) as a novel therapeutic approach for the treatment of schizophrenia.