2019 Schaefer Scholars Announced
Four researchers at the Vagelos College of Physicians and Surgeons have been named 2019 Schaefer Research Scholars: Swarnali Acharyya, PhD; Mohammad Amani, PhD; Luke Berchowitz, PhD; and Christian Lüscher, MD.
The Schaefer Research Scholars Program at VP&S supports research scientists who have distinguished themselves in the science of human physiology and whose proposed research should illuminate the field. Scholars are nominated by a committee of distinguished research faculty and selected by the VP&S dean. Each scholar receives an award of $50,000 in discretionary funds and up to $200,000 in direct costs to fund research projects. The program is made possible through an endowment from the Dr. Ludwig Schaefer Fund.
The 2019 Schaefer Scholars—two VP&S faculty members and two visiting professors—and their projects:
"Identifying Mechanisms of Brain Metastasis"
Brain metastasis is a common, incurable complication of many cancers and is associated with a severe deterioration of cognitive and motor function. Brain metastasis is 10 times more common than primary brain tumors. Though treatments may modestly slow the progression of brain metastasis, responses are often transient and relapse rate is high. Understanding how cancer cells invade the brain and grow in its microenvironment is key for developing mechanism-based therapies that are effective against metastatic tumors.
Acharyya is approaching the problem by developing new animal models of brain metastasis using human cancer cells from cancer patients. Her research has identified proteins that accumulate within these cancer cells and suggests that these proteins may mediate metastasis to the brain. Using genetic strategies, the Acharyya laboratory is altering the expression of these proteins to learn about their signaling mechanisms within the brain and how these proteins function to mediate brain metastasis.
Since her recruitment to VP&S in 2014, Acharyya has investigated mechanisms of metastasis in multiple types of cancer and identified a critical mediator of cancer-induced cachexia. She has received several honors, including a Herbert Irving Scholar Award, American Cancer Society Research Scholar Award, DoD Lung Cancer Career Development Award, DoD Breast Cancer Breakthrough Award, Irma T. Hirschl Career Scientist Award, and a Susan G. Komen Career Catalyst Award.
"Toward a Molecular Understanding of Intracellular Amyloid Regulation"
Amyloids are fibrous protein aggregates that have been linked to a large number of human diseases, including Alzheimer’s and Parkinson’s diseases. Though reversal and clearance of these aggregates were classically believed not to occur, some cells have developed mechanisms to regulate the assembly and disassembly of similar amyloid-like structures. Elucidating these mechanisms may lead to novel treatments that target and reverse pathological aggregation.
Previous work by Berchowitz has shown that budding yeast cells regulate the assembly and clearance of amyloid-like structures during meiosis. Furthermore, ground squirrels accumulate and then reverse amyloid-like structures during the cycle of hibernation by an unknown process. For his Schaefer project, Berchowitz will study the mechanisms underlying the assembly and reversal of amyloid-like structures in ground squirrel neurons differentiated from induced pluripotent stem cells and in budding yeast models.
Berchowitz is an experienced yeast biologist, publishing extensively on meiotic mechanisms including the detailed analysis of amyloid-like structure assembly and clearance. He has continued this work since his recruitment to VP&S in 2016. Berchowitz has received multiple awards, including the Amyloidosis Foundation Donald C. Brockman Memorial Research Grant, Alice Bohmfalk Charitable Trust Award, and a MIRA award from the National Institutes of Health.
Mohammad Amani, PhD
"Synaptic Effects of ATF4 Regulation in Alzheimer's Disease"
Amani’s project will provide insight into the role of ATF4 in Alzheimer’s disease and whether targeting this pathway may have therapeutic benefit.
Synaptic plasticity, the process of strengthening or weakening connections between neurons, is widely believed to be the mechanism that underlies memory formation and loss. Mechanisms that underlie synaptic plasticity have been shown to be disrupted in Alzheimer’s disease, providing a potential target for therapy development. One such process involves the regulation of synaptic plasticity by ATF4, an important transcription factor shown to control learning and memory. It is unclear, however, if ATF4 expression is altered in Alzheimer’s disease and its respective role in the pathophysiology.
Amani will evaluate whether modulating the expression of ATF4 within an animal model of Alzheimer’s disease normalizes its behavior and/or its electrophysiological profile. At Columbia, Amani will carry out his research in collaboration with Michael Shelanski, MD, PhD, a leader in the Alzheimer’s research community who has developed tools to modulate ATF4 expression in vivo.
As a neurobiologist with extensive experience using electrophysiological techniques, Amani has investigated the impact of disease and pharmacological manipulation on synaptic plasticity and memory. His previous work has identified possible pharmacological agents to treat Alzheimer’s disease and characterized the effects of amyloid aggregates on synaptic plasticity.
"Dopamine and Serotonin Modulation of Population Activity in Ventral and Dorsal Striatum in Motivation and Anhedonia"
Behaviors such as addiction and depression may be affected by the neuromodulators dopamine and serotonin. However, knowledge of the regional targets of these neuromodulators in the brain that are involved with behavioral adaptation and their mechanisms of action remains incomplete.
Lüscher and his group’s recent publication in Nature highlights the underlying role of dopaminergic input within the striatum (a region in the brain residing in the basal ganglia) in compulsive behavior. His Schaefer project involves the use of animal models, genetically engineered to allow light stimulation or repression of dopaminergic and serotonergic neurons (through expression of excitatory and inhibitory opsins). While controlling the activity of these neurons, he will be able to visualize the response of their connections within the striatum, building on our understanding of the mechanism of neuromodulation in the striatum and its subsequent influence on behavior.
Lüscher has an extensive research background in the study of drug reinforcement and addiction. At VP&S, he will work with René Hen, PhD, who is a leading expert on the serotonergic governance of behavior. Lüscher has received many awards, including the Théodore Ott Prize from the Swiss Academy of Medical Sciences and the Betty and David Koetser Award for Brain Research.