Four Scientists Awarded Schaefer Research Scholarships
Four scientists at Columbia University Vagelos College of Physicians and Surgeons have received awards from the Schaefer Research Scholars Program, made possible through a bequest from Dr. Ludwig Schaefer. Each award consists of a $50,000 cash prize and up to $200,000 in direct research support.
Two awardees are full-time VP&S faculty and two are visiting faculty who are collaborating with VP&S faculty:
- Emily Mace, PhD, assistant professor of pediatric immunology (in pediatrics)
- Markus Siegelin, MD, associate professor of pathology & cell biology and a member of the Herbert Irving Comprehensive Cancer Center
- Etienne Jacotot, PhD, research director at INSERM (France) and visiting professor, Taub Institute (in the laboratory of Carol Troy, MD, PhD)
- David Roper, PhD, professor of biochemistry and structural biology at the University of Warwick (U.K.) and visiting professor of physiology & cellular biophysics (in the laboratory of Filippo Mancia, PhD) and microbiology & immunology (in the laboratory of Jonathan Dworkin, PhD).
Each year the program presents awards to four research scientists—two residing or working in the Americas and two residing or working outside the Americas—who have distinguished themselves in the science of human physiology and whose current work is of outstanding merit with significant academic distinction.
More information about each scientist and their projects:
"Drawing the roadmap of human natural killer cell development"
The human immune system is a direct regulator of survival and provides an essential defense against infection. Deregulation of the immune system can lead to a loss of these defenses and induce autoimmunity and other diseases. Innate immune cells are critical in their influence on the immune response, control of viral infection, and in the body’s fight against cancer. Elucidating the underlying cellular physiology that drives the generation and regulation of innate immune cells is paramount to the understanding of their biology and to ultimately creating therapies that treat their dysfunction.
Mace’s Schaefer project will utilize novel models of visualizing and studying human immune cells to identify how interactions between innate immune cells and their microenvironments determine innate immune cell fate. Understanding these mechanisms will aid in the predictability of transplant outcomes and in the generation of immunotherapies as well as better define the role of innate immune cells in the tumor microenvironment and the control of malignancy.
Mace is a developmental immunologist with over a decade of experience utilizing cell biological analyses to model innate immune cell development in vitro. She has published extensively on this topic and continued this work after her recruitment to Columbia in 2018. Mace has received multiple awards including the Caroline Wiess Law Fund for Molecular Medicine Scholar Award and the American Society for Hematology Junior Scholar Award.
"Epigenetic targeting of the Warburg effect leads to therapeutic vulnerabilities"
Glioblastoma multiforme is the most common primary brain tumor and it is a devastating and aggressive disease for which there is no effective cure. A promising area of therapeutic exploration in glioblastoma multiforme and other solid tumors is their dependence on a modified form of cellular metabolism. Uncovering the mechanisms that underly these unique metabolic changes is critical to the identification of possible new therapeutic targets.
Siegelin’s previous work has revealed potential epigenetic regulators of the modified metabolic processes found in glioblastoma multiforme. For his Schaefer project, he will disrupt these epigenetic regulators to uncover mechanisms that reprogram the metabolic processes in glioblastoma cells. He also will test whether these cells become susceptible to therapeutic intervention once reprogramed. Using both in vitro and in vivo models, this work aims to elucidate epigenetic mechanisms that may underlie metabolic changes in tumor cells, as well as test the therapeutic potential of novel targets.
Siegelin has over a decade of experience as a physician-scientist investigating cell death mechanisms in tumors and identifying novel treatments for glioblastoma and other resistant malignancies. He was recruited to Columbia University in 2013 and has published numerous articles on his research focus. He has received multiple awards including the HICCC Physician-Scientist Pilot Award, an American Brain Tumor Discovery Grant, American Brain Tumor Association Translational Award, and the AACR-NBTS Career Development Award for Translational Brain Tumor Research.
"Role and targeting of Caspase-2 in Alzheimer’s disease"
Alzheimer’s disease is a devastating disorder and a major cause of death worldwide. Caspase-2 has been linked to the cognitive decline seen in animal models of the disease and has been proposed as a potential therapeutic target. Caspase-2 is a protease enzyme implicated in a broad range of physiological functions and has potential roles in chronic and acute neurodegeneration. It has also been shown to drive synaptic dysfunction in Alzheimer’s disease, a key feature of this disease and many other types of dementia.
Jacotot previously developed novel Caspase-2-targeted animal models and pharmacological inhibitors that will selectively block its activity. His Schaefer project will utilize these inhibitors, along with genetic and microfluidic methods, to investigate the role of Caspase-2 in the pathophysiology of Alzheimer’s disease. He also will evaluate the protective effect of Caspase-2 inhibition in animal models of the disease and its potential as a possible therapy. His project will be carried out at Columbia in collaboration with Carol Troy, MD, PhD, a leader in the Alzheimer’s research community who has developed many tools to study Caspase-2 function.
Jacotot has over 25 years of experience studying basic and translational aspects of disease biology, publishing extensively on the effects of Caspase-2 inhibition in neurons, and patenting novel inhibitors. Jacotot has been a research director at INSERM since 2010, was awarded a visiting professorship at Imperial College London from 2009-2014, and was the co-founder and CEO of Theraptosis S.A.
"Molecular machines that synthesize the bacterial cell wall"
Antimicrobial resistance is a worldwide crisis in health care and discovering new antibiotics is paramount to the success of this battle. In bacteria, potential new antibiotic targets may lie within the multi-protein complexes that synthesize mesh-like extracellular polymer configurations that are essential for overall cellular structure and proliferation. Disruption of this synthesis process results in lysis of the cell or cessation of growth. However, the organization of the multi-protein complexes and the mechanisms that carry out the biosynthesis are poorly understood—knowledge that is key to uncovering targets for antibiotics.
As an internationally recognized expert in bacterial cell wall biosynthesis, antibiotic resistance, and cell division mechanisms, Roper has extensive experience in the analysis of molecular mechanisms and inhibition of enzymes involved in these processes. At Columbia, his Schaefer project will be carried out in collaboration with Filippo Mancia, PhD, and Jonathan Dworkin, PhD, and focus on the structural biology of the multi-protein complexes that synthesize the mesh-like extracellular polymer configurations that make up the bacterial cell wall. The aim of the project is to elucidate molecular mechanisms that mediate the function of these multi-protein enzyme complexes and understand their role in the assembly of the bacterial cell wall.
Roper’s background as a microbial biochemist and his over three decades of experience working on molecular mechanisms in bacteria and the discovery of new targets for antibiotics have led to extensive publications on these topics. Early data with his Columbia collaborators have already produced a preliminary structure of two protein complexes, and his Schaefer project will further illuminate the structural and mechanistic understanding of biosynthetic processes in bacterial structure and division.