P&S professors Piero Dalerba and Lei Ding and visiting professor Rob Lane have been named 2017 Schaefer Research Scholars.
The Schaefer Research Scholars Program at P&S supports research scientists who have distinguished themselves in the study of human physiology. Scholars, who are nominated by a committee of distinguished research faculty and selected by the P&S dean, receive an award of $50,000 in discretionary funds and up to $220,000 in direct costs to fund research projects. The program is possible through an endowment from the Dr. Ludwig Schaefer Fund.
The 2017 Schaefer Research Scholars and their projects:
Piero Dalerba, MD, assistant professor of pathology & cell biology
Project: “Using ‘Single-Cell RNA-seq’ to Generate a ‘Transcriptional Atlas’ of the Human Colon Epithelium and Resolve the Cellular Origins of Human CDX2neg Colon Carcinomas”
Dr. Dalerba recently identified an extremely aggressive subtype of human colorectal malignancy defined by the lack of a protein called CDX2. These tumors are associated with an increased risk of relapse, reduced patient survival, an increased resistance to specific types of anti-tumor drugs, and a gene expression signature that is characteristic of intestinal stem cells.
Dr. Dalerba’s project is aimed at identifying the cell population from which human CDX2neg colon cancers originate and at determining whether this population is characterized by stem cell properties. He will use new single-cell genomics technologies to analyze the gene expression properties of hundreds of individual cells purified from human intestinal tissues. He will use the results to generate a “molecular atlas” of the various cell types that are found in the healthy colon epithelium. This molecular atlas will help guide the discovery of new surface markers for the differential purification of human intestinal stem cells.
Dr. Dalerba was recruited to P&S in 2014 and now directs a research laboratory at the Herbert Irving Comprehensive Cancer Center of Columbia University Medical Center. He is a pioneer in the use of single-cell genomics methodologies to study the cell composition of human tissues, both normal and cancerous, and in the study of human “cancer stem cell” populations. He has been granted several patents as well as research awards, including a 2012 Young Investigator Award from the National Comprehensive Cancer Network and a 2016 Runyon-Rachleff Innovation Award from the Damon Runyon Cancer Research Foundation.
Lei Ding, PhD, assistant professor of rehabilitation & regenerative medicine and of microbiology & immunology
Project: “Understanding the Liver Hematopoietic Stem Cell Niche”
Hematopoiesis is the process by which billions of new blood cells are generated daily from hematopoietic stem cells (HSCs). These stem cells play critical roles in the generation, repair, and homeostasis of the blood and immune system and are the main component in bone marrow transplantations used to treat a number of hematologic diseases such as leukemia, bone marrow failure syndromes, and anemia.
Dr. Ding identified certain cell types that compose the HSC microenvironment, or stem cell niche, which is important for maintaining the cellular properties of HSCs. In adults, the niche is localized in the bone marrow, but in the fetus, the major hematopoietic organ is the liver, where the niche is likely very different. The adult liver also can support HSCs to mitigate hematopoietic stresses, such as anemia and infection. Dr. Ding’s proposed Schaefer project is aimed at determining how fetal and adult liver niches comparatively regulate hematopoietic stem and progenitor cells. His findings will significantly advance our understanding of HSC regulation by the niche and aid in developing novel methods to better use HSCs to treat hematologic diseases.
Dr. Ding was recruited to P&S in 2013 and was the top choice in the international search for new stem cell recruits to the Columbia Stem Cell Initiative. His contributions to the hematopoietic stem cell field, a high-profile and competitive area, are widely recognized. He also has received multiple awards including fellowships from the Helen Hay Whitney Foundation and was named a Rita Allen Foundation Scholar.
Rob Lane, PhD, head of the dopamine pharmacology laboratory and R.D. Wright Biomedical Fellow, Monash Institute of Pharmaceutical Science, Monash University, Melbourne, Australia, and visiting professor in psychiatry at P&S
Project: “Mechanisms of Biased Agonism: Identifying Drug-Specific Dopamine Receptor Signaling Complexes in the Brain.”
Dr. Lane’s research focuses on a large family of G protein-coupled receptors that control critical processes in the nervous system. These proteins are the target for one-third of medicines in the clinic. Unfortunately, the discovery of new therapeutics that target these receptors remains challenging, often because the action of such drugs at the right receptor protein but in the wrong cell or tissue can cause undesirable side effects. This means that the current treatments for many diseases such as schizophrenia and Parkinson’s remain suboptimal.
A phenomenon called biased agonism may guide the discovery of new drugs that bind the target receptor protein and selectively activate therapeutically beneficial signaling pathways over those that cause the undesirable side effects of current therapies. The promise of biased agonism, then, is tissue- or cell-specific therapies with fewer side effects. Dr. Lane’s work aims to reveal how drugs with different pathway-selective actions may cause different effects in the body, the key challenge for the development of such novel therapies.
Dr. Lane’s research perfectly complements Columbia University’s efforts to understand the role of dopamine signaling in neuropsychiatric disorders and their therapies. His studies, done In collaboration with Jonathan Javitch, MD, PhD, the Lieber Professor of Experimental Therapeutics (in Psychiatry) and professor of pharmacology at Columbia and chief of the Division of Molecular Therapeutics at New York State Psychiatric Institute, will provide new insight into the nervous system and may facilitate the identification of new treatments for neuropsychiatric disorders with fewer undesired side effects.