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through tissue regeneration and the treatment of disease continues to grow, the majority of current strategies rely on outdated technology initially developed and optimized for starkly different applications.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.
Alvin Liu, PhD (Urology)
We work on solving the cancer problem. For prostate cancer, we have developed a multi-marker urine test for early detection. We have generated a human:mouse chimeric antibody that targets eAGR2, a cancer-specific cell surface antigen present on many solid tumor types including prostate, pancreatic, lung, breast, colorectal, oral. Antibodies bind to eAGR2+ cancer cells and recruit immune components to kill the target as in our normal immune response. A chimeric antibody has the mouse antigen binding domain coupled to human effector domain that interacts with human immune factors such as T cells and complement proteins. We are carrying out reprogramming of cancer cells to determine if cancer stem cells exist because these cells are hypothesized to cause tumorigenesis. This study has uncovered a possible link between the more treatable adenocarcinoma and untreatable small cell carcinoma (found most commonly in lung cancer). Another study involves the signaling/communication between epithelial (normal counterpart of cancer) and stromal cells, the latter regulate epithelial differentiation. We found a number of stromal cell genes missing in prostate and bladder tumors.
Our goal is to find a cure for cancer. This requires a molecular understanding of cancer development and progression. And, to develop a strategy for cancer vaccination since cell surface eAGR2 is specific to cancer (normal cells have iAGR2, intracellular vs. extracellular, in the interior). A primed immune system will eliminate any newly arisen cancer cells with eAGR2 while normal cells with iAGR2 will not be affected.
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.