Extracellular Regulation of Metabolism Laboratory - Human Performance Clinical Research Laboratory

Our laboratory is interested in understanding how cells, tissues, and organs communicate. In particular, we study small cell-derived particles called extracellular vesicles, or EVs. EVs can be released from any cell in the body and have been implicated in cancer, metabolic and cardiovascular diseases. We study how, when, and why EVs are released from skeletal muscle during exercise or in response to different diets. Our long-term goal is to identify EV-based therapies to prevent and/or treat metabolic disease.

Our Work

Human Subjects Research

We study how EVs change in response to exercise, food or diseases like obesity in the blood of human subjects. Thus far, these projects have been retrospective, meaning we obtain blood samples studies have been performed by other research groups. This is advantageous because it allows us to analyze the EVs in relation to demographic and physiological data. In the future, we plan to conduct prospective studies in which we recruit and study human subjects in our laboratory using dietary, physical or pharmacological interventions.

Model Systems Research

An important piece of our research program is the use of mice and cultured cells. We create genetically engineered mice to study where EVs are coming from and how their secretion is regulated. To do this, we created a mouse where different cell types (i.e. skeletal muscle myocytes) are “color-coded” so we can track the origin of EVs from different cells in vivo. We have also developed an ex vivo method where we place cells or tissues in a dish and treat them with various chemicals to mimic exercise or overnutrition. We can also use chemicals targeting specific signaling pathways to try to identify the cellular mechanisms regulating EVs secretion.

Methods

We use both conventional molecular biology (i.e. western blotting and PCR) and highly specialized approaches to study EVs. For example, we use nanoparticle tracking analysis (NTA) to measure EVs size and abundance. This approach involves firing lasers at EVs and then using a very sensitive camera to measure how fast they move. Their rate of movement tells us their size, and the number of particles tells us their abundance. We also use flow cytometry, which as the name indicates, is designed for cells. Extracellular vesicles are much smaller (~100x) than cells, but we have developed a method that allows us to study EVs using this instrument. We use flow cytometry to define the origin of EVs (using the “color-coded” mouse described above) and analyze the composition of EVs using antibodies that target specific surface markers.

Principal Investigator Dan Lark, Ph.D.

Originally from the Chicagoland area, I took the scenic route through college. First failing as a music major, then as a business major, I dropped out of college and tried to find what I was passionate about. I began exercising and became enthusiastic about a career as a strength coach. I went back to school as an Exercise Science major at the University of Wisconsin – Milwaukee. At UWM, I was introduced to research first by studying elite athlete performance. On a whim, I helped out with a project studying rats that was aimed at developing a new therapy for diabetes. It was at this moment that I became fascinated biological mechanisms. From there, I pursued graduate studies at East Carolina University studying mitochondrial function. I went on to perform my postdoctoral fellowship at Vanderbilt University Medical Center where I studied the systemic regulation of blood glucose and energy expenditure using genetically engineered mice. I began at CSU in 2018 and opened my laboratory to focus on understanding how extracellular vesicles (EVs), small “hormone-like” particles circulating in the blood, contribute to metabolic disease. My approach to science is one of patience, creativity, and perseverance. Many times, the result of an experiment is “yes, but…” and those caveats are often the most interesting part of a project.

Education

2005, A.A.S., University of Wisconsin – Fond du Lac, Fond du Lac, WI
2008, B.S., Exercise Science, University of Wisconsin – Milwaukee, Milwaukee, WI
2010, M.S., Exercise & Sports Science, East Carolina University, Greenville, NC
2014, Ph.D., Bioenergetics and Exercise Science, East Carolina University, Greenville, NC

Daniel Lark – Assistant Professor in the Health and Exersice Sciences in the College of Healt and Human Sciences, June 23, 2018.

Doctoral Student Zack Valenti, M.S.

Hailing from the east coast, I completed my undergraduate degree in Exercise Science at Salisbury University, MD. It was during this time that I served as a research assistant with Dr. Scott Mazzetti on a project investigating whole-muscle energetic demands of concentric vs. eccentric muscle actions. Now infatuated with skeletal muscle physiology I sought out graduate programs that aligned with my research interests, leading me to Colorado State University’s Human Performance Clinical Research Laboratory under the cumulative mentorship of Dr. Karyn Hamilton and Dr. Ben Miller. During my master’s thesis, I conducted a project aimed at investigating the role of Nrf2 activation on mediating protein synthesis rates in C57BL6/J mice. This work sparked my interest in responses/adaptations to metabolic stress in skeletal muscle, which I am fortunate to be able to investigate in the ERM lab as I pursue my Ph.D. under Dr. Dan Lark’s mentorship. Currently, I am using my experiences in the wet lab/animal procedure room to develop an ex-vivo approach that allows our lab to investigate skeletal muscle extracellular vesicle secretion in response to various chemical stressors.

Zack Valenti, Ph.D. student in the ERM lab

Graduate Student Brittany Hayward, B.S.

I started college as a psychology major, thinking I wanted to help children process trauma. I then added an art major, thinking I would become one of the few full-time photographers for National Geographic. I quickly gave up on both of those dreams, upon the discovery of Health and Exercise Science. Once I found this major, my brain literally exploded. I found a world so immense and so thought-provoking, that even after five and a half years in this field, I have yet to spend one day bored. For my master’s thesis, I am investigating how exercise induces the secretion of extracellular vesicles, an area full of wondrous possibilities, proving over again every day, how exciting science can be.

Graduate Student Nick Hulett, B.S.

Nicholas Hulett graduated from Harding University with a B.S. in Exercise Science. Now in the M.S. program at CSU, he is interested in how extracellular vesicle response changes in response to an acute glucose challenge and if exercise modulates this response. When not in the lab, he can be found walking his dog Eiger or finding the hardest way to get on top of a piece of rock.

Nick Hulett, ERM Lab Technician, smiling in a forest

Research Associate Gabriella Hehn, B.S.

I graduated in 2019 with a degree in Biology. I worked at the HES department in the main office during my undergrad. It was here I was introduced to Dr. Lark’s Lab. I always wanted to work in a research lab, but the biology department focuses more on plants and animals, and I wanted to work in a lab that focused on people. My career goals include going back to nursing school and becoming an NP later in life. This is my first job after college as a Research Associate, and I have learned so much. I have really enjoyed working in the lab!

Gabriella Hehn, ERM Lab Technician with CAM the Ram

Human Performance Clinical Research Laboratory Extracellular Regulation of Metabolism Laboratory