Three Baylor College of Medicine faculty members, Dr. Blair Benham-Pyle, Dr. Steven Boeynaems and Dr. Hongjie Li, have been awarded the National Institutes of Health Director's New Innovator Award. The award, a part of the NIH Common Fund's High-Risk, High-Reward Research program, supports unusually innovative research from early career investigators. All three researchers will receive $2.4 million for their work.
Dr. Blair Benham-Pyle
Dr. Blair Benham-Pyle, assistant professor in the Stem Cell and Regenerative Medicine Center and the Department of Molecular and Cellular Biology, will study the regenerative mechanisms of the planarian flatworm, an invertebrate that asexually reproduces by breaking into pieces and regenerating the missing tissue. This process, made possible by an abundance of stem cells, seems to protect the worm from aging-related issues.
"In most vertebrate systems, repairing tissue leads to an increased likelihood of DNA damage and mutations that eventually lead to age-associated diseases or cancer," said Benham-Pyle, a member of the Dan L Duncan Comprehensive Cancer Center and a CPRIT Scholar. "But in the case of the worm, inducing regeneration actually makes it healthier. The worm makes injuries adaptive, rather than deleterious."
Benham-Pyle's lab has preliminary data indicating that when the worm begins to accumulate age-related damage and stem cell function declines, it induces asexual reproduction behavior. Through the process of whole-body regeneration, the worm returns to a healthy state. Because roughly 60% of the planarian flatworm genes have human homologs, Benham-Pyle believes that some of the mechanisms and signaling pathways that control the regeneration process may be conserved in humans.
"The signaling pathways in humans may be wired to respond to damage differently. If we can better understand those pathways, we can move one step forward in translating the worm's remarkable regenerative capacity to a human system," Benham-Pyle said.
Dr. Steven Boeynaems
Dr. Steven Boeynaems, assistant professor of molecular and human genetics at Baylor and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, will focus on the role of neuroinflammation in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease. In people with these conditions, the brain's immune cells enter a hyperinflammatory state in response to a build-up of protein clumps in the brain, leaving these cells unable to perform their normal support function for neurons and even harming them. After decades of these immune cells attempting to fight these proteins, the neurons eventually begin to die.
"We are starting to understand that the protein pathology in the brain triggers neuroinflammation because it mimics the molecular features of an infection. If you look at the structure of these proteins and how they interact with immune cells, it's the same as how bacterial and viral proteins would interact," said Boeynaems, a member of the Center for Alzheimer's and Neurodegenerative Diseases, the Dan L Duncan Comprehensive Cancer Center and the Therapeutic Innovation Center at Baylor and a CPRIT Scholar.
Building on preliminary findings in his lab, Boeynaems will study how neuropathology mimics infectious disease and how the innate immune system responds. He will study neutralizing mechanisms that bacteria use to hide from the immune system to explore whether it is possible to use similar strategies to intervene and calm down the immune response in neurodegenerative disease.
"Inflammation is involved in many other diseases, including autoimmune disease and cardiovascular disease," Boeynaems said. "We believe that the concepts we are studying here are going to be applicable across many different types of disease."
Dr. Hongjie Li
Dr. Hongjie Li, assistant professor in the Huffington Center on Aging and the Department of Molecular and Human Genetics, will study how aging affects the brain's communication with the rest of the body systems. These processes are disrupted by factors like stress, inflammation and metabolic disorders as we age. Using an innovative whole organism single-cell sequencing platform developed in his lab and cutting-edge machine learning methodologies, Li will work to construct aging trajectories for Drosophila, better known as fruit flies, which share many key aging pathways with humans.
"Aging is the cause of almost all chronic diseases," said Li, a member of the Dan L Duncan Comprehensive Cancer Center and a CPRIT scholar. "If we can better understand the fundamental mechanisms behind how aging affects brain-body communication, we can better design interventions to promote healthy aging."
Li's research will take a systemic approach to explore how peripheral tissues contribute to the decline of brain-body communication as we age. Preliminary studies in his lab have shown that neurodegeneration leads to functional decline of various peripheral cells and targeting peripheral tissues can modulate or improve function of the brain. In this project, Li aims to chart the first aging trajectories of a multi-cellular complex organism, a necessary step toward the goal of one day creating aging trajectories for individual humans.
"Different people have different aging trajectories and require different treatments and interventions as they age," Li said. "To unlock the potential for personalized interventions, we need a deep comprehension of the individual aging process."
