Jeremy Ducharme, Ph.D.
Post-doctoral Fellow, UF College of Public Health & Health Professions Department of Physical Therapy; UF Health Cancer Center
Abstract
The involuntary loss of body weight that occurs in many cancer patients is a condition called cachexia. This loss of body weight is due to the loss of skeletal muscle mass, which negatively impacts physical function, quality of life, treatment tolerance, and survival. Our research team has shown that skeletal muscles from people and mice with pancreatic tumors exhibit skeletal muscle damage, persistent immune cell infiltration, and impaired regeneration. These phenotypes may be influenced by the accumulation of senescent cells, which are cells that no longer divide but secrete inflammatory cytokines, chemokines, proteases, and growth factors known to negatively impact skeletal muscle. However, there is currently no comprehensive research investigating the accumulation of senescent cells in the skeletal muscle of tumor-bearing hosts, and thus no study that tests whether selectively targeting and eliminating senescent cells (senolytics) can prevent their accumulation and delay or inhibit cancer-induced muscle wasting. To address this gap, we collected muscles from mice with pancreatic tumors treated with and without chemotherapy. We observed an increase in several hallmark indicators of senescence at a time point that corresponds with the onset of cancer-induced skeletal muscle wasting, and this accumulation was further exacerbated by chemotherapy. These findings identify senescent cells in skeletal muscle as potential therapeutic targets for the treatment of cancer-induced muscle wasting. Our next series of experiments will build from this foundation, and we will administer a senolytic proteolysis targeting chimera against a protein that regulates cell division to test whether this treatment can prevent senescent cell accumulation and combat skeletal muscle wasting in the context of pancreatic cancer.
Speaker Bio
Dr. Jeremy Ducharme is a post-doctoral fellow in the Judge Laboratory at UF, studying the regulation of muscle mass and cancer-associated muscle pathology. He is completing his second year in the TICaRT program, where he has been working with Madison Carelock, a pre-doctoral fellow in the cancer biology concentration of the UF Graduate Program in Biomedical Sciences.
Florida’s State Academic Standards for Science
SC.912.L.16.8
Explain the relationship between mutation, cell cycle, and uncontrolled cell growth potentially resulting in cancer.
SC.912.L.16.10
Evaluate the impact of biotechnology on the individual, society and the environment, including medical and ethical issues.
SC.912.N.1.4
Identify sources of information and assess their reliability according to the strict standards of scientific investigation.
SC.912.N.1.7
Recognize the role of creativity in constructing scientific questions, methods and explanations.
SC.912.N.1.6
Describe how scientific inferences are drawn from scientific observations and provide examples from the content being studied.
SC.912.L.14.11
Classify and state the defining characteristics of epithelial tissue, connective tissue, muscle tissue, and nervous tissue.
SC.912.L.14.16
Describe the anatomy and histology, including ultrastructure, of muscle tissue.
