Completed Grants and Sponsored Research

The specific aim of this study is to identify small molecule compounds that target del7q clones in Shwachman Diamond Syndrome.

This will utilize CRISPR/Cas to knock down genes. This approach will address the potential limitations of offtarget effects engendered by siRNA screening approaches.

Aim: Support research on aplastic anemia with the goal of improving diagnosis and treatment. I designed the study and experiments, analyze the data, and wrote the papers.

Aim: Utilize induced pleuripotent stem cells to study clonal evolution in Shwachman-Diamond Syndrome. I designed the study and experiments and analyzed the data.

Aim: Investigate genomic markers to guide choice of therapy for aplastic anemia. I designed the study and experiments, analyzed the data, and am editing the paper manuscript.

Aim: Coordinate studies investigating common mechanisms and clinical complications shared between SCN and other neutopenia/ marrow failure syndromes. I served as a collaborator to review clinical records to determine study eligibility and field questions from referring physicians.

Aim: Investigate the role of SBDS in ribosome homeostasis. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Develop methods to expand autologous hematopoietic stem cells from Shwachman-Diamond syndrome patients to provide sufficient numbers of cells for mutational repair and for improved engraftment. I designed the experiments and analyzed the data.

Aim: Investigate whether short telomere length is associated with immunologic dysfunction in patients presenting with and without marrow failure. I clinically phenotyped patients with marrow failure for this study and recruited study subjects.

Aim: Utilize spermatogonial stem cell (SSC) transplantation to generate a canine model of Fanconi anemia. I served as administrative PI for this multi-PI grand and designed the experiments and analyzed the data for my project.

Aim: Examine the role of translational control of gene expression in a ribosomal disorder contributing to leukemogenesis via marrow stromal cell dysfunction. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Utilize engineered homing endonucleases to correct the mutations causing the inherited bone marrow failure syndrome Shwachman-Diamond syndrome (SDS) in SDS patient-derived iPS cells. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Establish a patient registry of clinical data and biological specimens to characterize the longitudinal natural history and molecular biology of Shwachman-Diamond syndrome. I organized and directed Registry activities.

Aim: Characterize the hematopoietic phenotype of a mouse model of SDS. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Work with the Severe Chronic Neutropenia Registry to establish international studies of Shwachman-Diamond syndrome. I directed the development of the Shwachman Diamond Syndrome Registry and Repository.

Aim: Study the signaling pathways leading from ribosomal protein insufficiency to p53 activation through 5’TOP translation regulation. I performed the studies knocking down ribosomal protein gene expression in primary human CD34+ cells and assessed effects on p53 activation.

Aim: Evaluate the effect of HDAC inhibitors on ribosome biogenesis and hematopoiesis. These compounds were identified as strong and reproducible hits in the unbiased chemical library screen in yeast. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Study the translational control of gene expression during hematopoiesis. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Support the Fourth International Congress on Shwachman-Diamond syndrome to discuss the latest clinical and research advances from multiple medical and scientific disciplines. I wrote the grant, worked with Dr. Grand to organize the conference, and wrote up the conference summary.

Aim: Investigate diagnostic and therapeutic applications of the FANCD2 activation assay. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Understand the molecular pathogenesis of Shwachman Diamond syndrome. I designed the study and experiments, analyzed the data, and wrote the papers

Aim: Develop a system of care for assessment and education, regional outreach to caregivers and families, and data collection to improve care for patients with Diamond Blackfan Anemia. I served as director for Boston Children’s Hospital Center of Excellence for Diamond Blackfan Anemia.

Develop and conduct clinical trials to correct congenital disease of the human hematopoietic stem cell. Project 5 focused on gene replacement for marrow failure syndromes. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Investigate pathways regulating myelopoiesis and malignant transformation. I designed the experiments, analyzed the data, and wrote the papers.

Aim: Establish a clinical program to improve the care of patients with marrow failure and to develop resources for basic research on marrow failure. I developed a Bone Marrow Failure program integrating clinical and research activities.

Identify signaling pathways regulating apoptosis. I designed the study and experiments, analyzed the data, and wrote the papers.

Aim: Investigate the regulation of apoptosis using a cell-free system. I designed the study and experiments, analyzed the data, and wrote the papers.