Nancy Allbritton, MD, PhD (Bioengineering)
Research in my laboratory focuses on the development of novel methods and technologies to answer fundamental questions in biology & medicine. Much of biology & medicine is technology limited in that leaps in knowledge follow closely on the heels of new discoveries and inventions in the physical and engineering sciences; consequently, interdisciplinary groups which bridge these different disciplines are playing increasingly important roles in biomedical research. Our lab has developed partnerships with other investigators in the areas of biology, medicine, chemistry, physics, and engineering to design, fabricate, test, and utilize new tools for biomedical and clinical research. Collaborative projects include novel strategies to measure enzyme activity in single cells using microelectrophoresis innovations, to build organ-on-a-chips particularly intestine-on-chip, array-based methods for cell screening and sorting. An additional focus area is the development of software and instrumentation to support these applications areas. The ultimate goal is to design and build novel technologies and then translate these technologies into the marketplace to insure their availability to the biomedical research and clinical communities to enable humans to lead healthier and more productive lives.
Cole DeForest, PhD (Chemical Engineering)
While the potential for biomaterial-based strategies to improve and extend the quality of human health through tissue regeneration and the treatment of disease continues to grow, the majority of current strategies rely on outdated technology initially developed and optimized for starkly different applications. Therefore, the DeForest Group seeks to integrate the governing principles of rational design with fundamental concepts from material science, synthetic chemistry, and stem cell biology to conceptualize, create, and exploit next-generation materials to address a variety of health-related problems. We are currently interested in the development of new classes of user-programmable hydrogels whose biochemical and biophysical properties can be tuned in time and space over a variety of scales. Our work relies heavily on the utilization of cytocompatible bioorthogonal chemistries, several of which can be initiated with light and thereby confined to specific sub-volumes of a sample. By recapitulating the dynamic nature of the native tissue through 4D control of the material properties, these synthetic environments are utilized to probe and better understand basic cell function as well as to engineer complex heterogeneous tissue.
Zhijun Duan, PhD (Medicine/Hematology)
Our research activities focus on deciphering the structure-function relationship of the genome to understand the molecular mechanisms underlying human development and tumorigenesis. It is increasingly recognized that the genetic materials, i.e., the genomic DNA, in human cells are nonrandomly organized into nested hierarchy in the three-dimensional (3D) space of the nucleus and this spatial organization critically impacts human health and disease, including cancer. Defects in the 3D genome organization have been observed in a wide spectrum of human diseases. Over the past years, we have developed a series of cutting-edge genomic tools for delineating the 3D genome organization globally or locally.
In addition to developing innovative technologies, we are using these tools to investigate how the 3D genome organization goes wrong in blood disorders. Nuclear dysplasia, i.e., abnormal changes in the size and shape of the nucleus, such as hyper-segmented neutrophils, hypolobated neutrophils and acquired Pelger–Huët anomalies (PHAs), is a hallmark for the diagnosis of many hematologic disorders, such as myelodysplastic syndromes (MDS). MDS are a group of clonal disorders of hematopoietic stem and progenitor cells. Characterized by dysplastic hematopoiesis, cytopenia and increased risk of progression to acute myeloid leukemia (AML), MDS remains a poorly treated, life-threatening disease. It remains unclear how the nuclear dysplasia that defines these disorders relates to MDS pathogenesis. To understand how 3D genome disruption may lead to MDS, we are using population-based and single-cell assays to identify abnormal features of the 3D genome and cis-regulatory landscapes in MDS blood cells, with the goal to provide new pathophysiological insights that has the potential to pave the way for developing better MDS diagnostics and therapeutics.
Marshall Horwitz, MD, PhD (Pathology)
The Horwitz laboratory has a longstanding interest in genes and mechanisms leading to hematological malignancy. More recently, the lab has focused attention on using somatic mutations to infer cell lineage in order to better understand how stem cells contribute to development, tissue regeneration, and cancer.
Masaoki Kawasumi, MD, PhD (Medicine/Dermatology)
Our research focuses on UV-induced DNA damage responses and skin cancer development. More recently, we study epigenetic aspect of skin differentiation and skin cancer evolution, investigating what DNA/histone modifications in hair follicle stem cells (the origin of skin cancer) contribute to the development of different subtypes of skin cancer. Our long-term goal is to better understand epigenetic mechanisms in hair follicle stem cells and cancer and use the fundamental knowledge to prevent and inhibit skin diseases including skin cancer.
Stephen Plymate, MD (Medicine/Gerontology and Geriatric Medicine)
Our lab focuses on prostate cancer, specifically we are interested in the targeting of prostate cancer stem cells that lead to tumor regrowth following anti androgen receptor therapy. We are especially interested in the switch between oxidative phosphorylation and glycolysis as an energy source in promoting growth. To this end we have developed specific small molecule inhibitors of glycolysis that are on track for phase 1 clinical trials.
Christina Termini, PhD (Fred Hutch)
Our laboratory aims to understand how the adult blood system regenerates after damaging stressors like radiation and chemotherapy and how these processes can be hijacked during malignant transformation. Our research melds basic cell biology, regenerative medicine, and cancer biology and uses quantitative microscopy, flow cytometry, and transgenic mouse models to build a multi-scale understanding of blood regeneration. Our goal is to identify new mechanisms to support healthy blood recovery and target cancer stem cells to eventually translate for clinical applications.
Xiaoming Yang, MD, PhD (Radiology)
Dr. Xiaoming Yang’s research team is focusing on fully applying the advances of modern imaging modalities to medicine, primarily developing new image-guided interventional techniques to monitor and guide stem cell and gene therapies, as well as immunotherapy of life-threatening diseases, such as atherosclerotic cardiovascular disease and different cancers.