A Career Reflection

Sandra G Velleman^*

• The Ohio State University, Columbus, United States

To be asked to write an opinion paper as part of the Frontiers in Avian Physiology, Lifetime Achievements Topic is an honor. In thinking about this paper and what research area I should focus on, I began to reflect on my career as a scientist, which commenced over 40 years ago, I thought of all the mountains and detours which had to be overcome, and opportunities along the way. With the current challenging times to pursue scientific research, I decided instead of writing an opinion paper on a specific research topic to provide a career perspective outlining my scientific journey.My interest in science started as a young girl growing up outside of Boston. When I was 6 years old, I proudly announced to my mother that I was going to be a veterinarian. I always gravitated to animals and was passionate about biological science. My mother helped fuel these interests with having a membership at the Museum of Science in Boston. Every Saturday, I would attend science classes followed by a visit to their library to select books for us to read together during the week. I still remember the instructor's name and some of the demonstrations done to illustrate scientific concepts. The time spent at the Museum of Science helped build my scientific passion. In school, I was placed in the honors science curriculum and took 10 th grade biology in 9 th grade. I was so fortunate to have a teacher who recognized my research skills. One day, she told me I was not going to be a veterinarian but a research scientist. I did not even know what a research scientist did and to be honest I was crushed. She signed my yearbook saying, "My budding scientist." At the time, I thought I would show her when I became a veterinarian. She saw something in me that I did not know and am forever grateful to her for planting a research scientist seed in my head.My undergraduate studies could simply be stated; she obtained her BA degree from Boston University with distinction in Biology in 1981. This statement would severely underrepresent this transformative period of my life. I was fortunate to take Cell Biology with a new Assistant Professor, Dr. Robert E. Hausman. I loved the Cell Biology course and was excited to attend lecture and learn as much as possible. One day, I finally had the courage to go to Dr. Hausman's office hours to ask if I could change advisors to him. The meeting changed my life. In addition to him becoming my advisor, he asked if I would like to work in his lab during the summer to help set it up. At the end of the summer, Dr. Hausman asked if I would like to apply for the research honors program. Like 9 th grade, I had someone seeing something in me that I did not recognize. My undergraduate research was on prostaglandin E1 during embryonic muscle development resulting in my first peer reviewed research publication in Biophysical Biochemical Research Communication in 1981 (Hausman and Velleman, 1981). More importantly, my lifelong interest in cellular communication mechanisms leading to tissue and organ formation was formulated. Opportunities often present themselves as minor steps in your life but can result in a new life direction. I am not sure where my life would be if I had not gone to Dr. Hausman's office hours. My life certainly would have been different and that is all I know.To further pursue cellular communication, my interest evolved into the new area of how the extrinsic environment outside the cell, the extracellular matrix, affected cellular behavior. I pursued my doctoral studies with Dr. Paul F. Goetinck at the University of Connecticut on the role of the extracellular matrix environment in avian limb development. After completing my doctoral studies in 1986, I was desirous of learning new emerging molecular biology techniques to study human diseases involving the extracellular matrix. To reach this goal, I was accepted as a National Institute of Health postdoctoral trainee at the University of Pennsylvania Medical School Connective Tissue Research Institute. During my doctoral studies, I had thought that I wanted to leave academia and pursue osteoarthritis work in a company. Gaining molecular biology skills was essential. However, I realized working with humans especially children presenting with various connective tissue disorders was very different than a research animal. It troubled me to witness children with severe connective tissue disorders like osteogenesis imperfecta. After much deliberation, I decided I did not have the appropriate emotional make up for the career I had thought was my future direction and needed a new path. Another opportunity presented itself and was a hidden life-changing pathway for me. At the University of Connecticut, an NIH program project grant with the Health Center was awarded and they needed someone to head the animal component of the research. It was explained to me with much chagrin that I would be in the Animal Science Department which was part of the College of Agricultural Sciences. My previous research had used an avian model, but I was always part of a biology department not one focused on domestic animal research. I agreed to the postdoctoral position with the option of developing my own research program for my future. McFarland if he thought satellite cells could be regulated by the extracellular matrix. Extracellular matrix, at that time, had been only identified in connective tissue and muscle was not a connective tissue. My gut instinct was that extracellular matrix may be an important component to non-connective tissues. I took a big risk, but Dr. McFarland was excited about collaborating with me on this. Hence, another life changing opportunity through attending a meeting and asking a question. In 1998, I published our research results demonstrating avian breast muscle satellite cells produce their own extracellular matrix (Velleman et al., 1998). This was a groundbreaking finding and completely opposed current dogma. We now know, the extracellular matrix is in all tissues and organs regulating biological homeostasis, growth, maintaining structural organization, and regeneration. My message here is to hold onto your beliefs even if established findings oppose them, you may be adding significant knowledge.In 1995, I transitioned into a tenure track Assistant Professorship in the Animal Sciences Department of The Ohio State University. I was promoted through the ranks and in 2022 received the honorific title of Distinguished Professor of Food, Agricultural, and Environmental Sciences in Animal Sciences. In 2024, I retired and am now a Professor Emeritus in the Animal Sciences Department. During my tenure at both University of Connecticut and The Ohio State University, the greatest joy has been impacting the lives of those I trained. My goal was to provide opportunities to others like those that made such a huge difference in my life trajectory. My undergraduate and graduate students, and postdoctoral researchers are my legacy.During my career, I published over 215 peer reviewed research publications, 8 book chapters, and have co-edited 8 books. Of my discoveries, the following are the ones which I deem most important: Extracellular matrix includes the collagens, proteoglycans, and non-collagenous glycoproteins and were thought to be produced by only connective tissue cells important in the structural support of tissues like bone and cartilage. Non-connective tissues like muscle were not thought to produce extracellular matrix proteins. In 1998 (Velleman, 1998), my laboratory was the first to show that breast muscle satellite cells synthesized extracellular matrix heparan sulfate proteoglycans. Heparan sulfate proteoglycans are a group of extracellular matrix macromolecules linking muscle cells to their extrinsic environment and regulating growth through fibroblast growth factor 2 signal transduction. This was one of the first demonstrations of an extracellular matrix protein being synthesized by a non-connective tissue cell type and having a function beyond just structural support. Subsequent studies through the years focused on 2 families of heparan sulfate proteoglycans, syndecans and glypicans, and how they differentially regulate breast muscle cell proliferation and differentiation. Muscle growth in poultry occurs through the formation of myofibers or hyperplasia of myoblasts with myoblasts fusing to form multinucleated myotubes that mature into muscle fibers and muscle fiber bundles. After hatch, all muscle growth is from satellite cells donating their nuclei to existing muscle fibers resulting in the enlargement of myofibers through hypertrophy. Although commonly thought of as a homogenous single cell population, satellite cells are composed of multiple populations with differing proliferation and differentiation in poultry. Research we conducted has shown that growth selection in poultry has altered the types of satellite cells present in breast muscle and their biological activity (Velleman, 2022;Xu et al., 2023;Xu and Velleman, 2023). In broilers, satellite cell proliferation and differentiation has decreased with growth selection whereas the opposite has occurred in meat-type turkeys (Xu and Velleman, 2023). Decreased satellite cell proliferation and differentiation especially in broilers maybe associated muscle fiber degenerative myopathies like Wooden Breast. The satellite cell is the cell type responsible for the repair and regeneration of myofibers which is likely suppressed with decreased satellite cell biological activity. Feed restrictions are used by the industry and newly hatched chicks and poults can be exposed to hot and cold temperatures during handling and transportation. In addition, to a potential to reduce final breast muscle weight, these extrinsic stimuli immediately after hatch can also change the expression of muscle-specific genes and cause the conversion of the satellite cells to an adipogenic cell fate increasing fat within the breast muscle (Velleman et al., 2010(Velleman et al., , 2014a,b),b). Xu et al. (2021) showed proliferating satellite cells are more sensitive to temperature than differentiating satellite cells in the expression of adipogenic genes. Immediately after hatch, satellite cells are rapidly proliferating increasing their responsiveness. Selection for growth in turkeys has increased the thermal sensitivity of satellite cells. When satellite cells have their highest mitotic activity immediately after hatch with greater proliferation taking place, this is the time that the satellite cells can express adipogenic genes, which may significantly affect the composition of the breast muscle and its morphological structure. A key finding from my research is that when feed restrictions are administered the first week post-hatch increased intramuscular lipid accumulation occurs in the market age breast muscle. If the feed restriction is done the second week post-hatch after the period of maximal satellite cell activity increased intramuscular fat accumulation was eliminated in the market age breast muscle. Commercial turkeys are produced by crossing a sire line usually selected for greater muscling and growth. During studies of muscle development in several line crosses, it was observed that breast muscle morphology of the offspring crosses always was the same as the female parent around market age (Velleman and Nestor, 2004). These findings indicated maternal inheritance of breast muscle morphological structure. This was one of the first observations of maternal inheritance influencing a trait of economic importance in a domestic animal.The most appropriate way to summarize my career is one of others recognizing talent in me and providing opportunities. For those early in their career always remain open to new paths. A new path might not be presented as a dramatic modification, but perhaps something subtle in nature. As a professional, I have tried to make a difference in the lives of my students by presenting them with new chances and adding novel information to the knowledge database. I always have tried my best and given a 100% effort into all endeavors.