xDr Skaug – Connecting the dots of Scleroderma Research

xDr Skaug – Connecting the dots of Scleroderma Research

Dr Skaug provides Rheumatology care and consultation at the UT Professional Building and Memorial Hermann Hospital in the Texas Medical Center and at Lyndon Baines Johnson Hospital within the Harris Health system. After school Dr Skaug was set on becoming a physician. Upon undertaking his undergraduate degree, he began to appreciate the tremendous complexity of biology, physiology and human diseases. Through participation in undergraduate research projects he developed an admiration for the challenging yet deeply gratifying process of scientific discovery. He became particularly fascinated by the processes of immunity and inflammation. This experience drove Dr Skaug to not only become a physician but to pursue a research qualification as well. During his time at UT Southwestern he was drawn to the work being done in the lab of Dr Zhijian which took a creative but rigorous approach to uncovering the molecular mechanisms that regulate the immune system. Training here gave Dr Skaug invaluable experience.  State of the art techniques he learnt allow him to better dig beneath the surface of biological challenges to gain knowledge that will help to answer the big research questions of today. He built on this strong foundation at UT Health Science Center in Houston where he completed his training in rheumatology and where he later joined the faculty in 2018. More than Skin Deep Scleroderma, also called systemic sclerosis is disease that affects connective tissues. It is a complex systemic autoimmune disease with abnormalities occurring in both the innate and adaptive immune systems. The symptoms vary from patient to patient but generally results thickening of the skin, scar tissue on organs such as the lungs and kidneys and thickening of blood vessels leading to high blood pressure and tissue damage. The effects from this condition range from very mild (limited skin involvement with minimal systemic involvement) to life threatening (widespread skin involvement accompanied by internal organ involvement). Pulmonary fibrosis [interstitial lung disease (ILD)] and pulmonary arterial hypertension (PAH) cause more than half of all scleroderma related deaths. Prompt and proper diagnosis and treatment by qualified physicians is key to minimize the symptoms of scleroderma and lessen the chance for irreversible damage. Although it is known that scleroderma involves an overproduction of collagen the exact cause or causes have not yet been identified. Currently there is no cure and treatments tend to be geared towards individual symptomatic relief. Dr Skaug’s research is focused on identifying mechanisms that drive dysfunction of the immune system resulting in scleroderma. A Sample of Things to Come At UT Health Science Center a scleroderma research program led by Dr Maureen Mayes and Dr Shervin Assassi, features a large and diverse group of systemic sclerosis patients, many of whom travel across Texas or from neighbouring states. These patients, along with their friends and family have not only given of their time but have also provided numerous biological samples in order to support scleroderma research. This has allowed the research program to take vital steps towards characterizing the molecular profile of systemic sclerosis. Dr Skaug believes that the involvement and leadership of senior faculty members with years of experience along with the special cohort of patients makes UT Health Science Center the right environment to pursue his research goals. Here he hopes to begin to close the significant gaps that remain in understanding scleroderma as well as ensuring the unmet needs of patients are addressed. Two Degrees are Better than One Being both an MD and PhD, a dual degree he was awarded in 2013, gives Dr Skaug the ability to see the real-life applications of research. This provides him unique opportunity to gain insight into what this condition means to the patients that have it. Understanding how lack of information in certain areas of research affects those with autoimmune conditions inspires this physician and researches to keep pushing for answers that will lead to improved treatments and maybe even a cure. A Rogue Gene Most patients with scleroderma do not have a relative with the condition nor do their children get the condition. Therefore, it is unlikely that scleroderma has a definitive genetic cause. That being said research has indicated that there are genetic factors that increase an individual’s susceptibility to developing the condition. Previous research in the division (Mayes et al., Am J Hum Genet., 2014) identified a gene called deoxyribonuclease 1-like 3 (DNASE1L3), that when functioning incorrectly acts as a risk factor for developing scleroderma. Dysfunction of this gene appears to also be a risk factor for other autoimmune diseases including, lupus, vasculitis, and rheumatoid arthritis, suggesting that DNASE1L3 is important for maintaining proper function of the immune system.  In humans this gene codes for an enzyme called deoxyribosenuclease gamma. Apoptosis is a form of programmed cell death, or “cellular suicide.” It is a normal process in the life cycle of a cell and as such it is different from necrosis, in which cells die due to injury. Apoptosis is an orderly process in which the cell’s contents are packaged into small packets surrounded by a membrane for “garbage collection” by immune cells. Deoxyribosenuclease gamma facilitates the breakdown of DNA by hydrolyzing it during apoptosis. A Work in Progress Based on work published by other investigators and preliminary data from their own research Dr Skaug is planning on focusing on two key areas. First, using blood samples from volunteer systemic sclerosis patients and samples from healthy controls, the team are planning on measuring the role of DNASE1L3 in the clearance of DNA that comes from cells that have died during normal cell turnover.  Secondly, they will be measuring the effects of excess DNASE1L3-substrate DNA (the DNA on which the enzyme acts) on immune cell function, to determine whether DNASE1L3 dysfunction contributes to the imbalanced immune system commonly observed in systemic sclerosis patients. “During my time as an ANRF scholar my main goal is to define the downstream biochemical and immunologic effects of this DNASE1L3 genetic variant in the context of systemic sclerosis pathogenesis. Shedding light on an important and incompletely understood aspect of autoimmunity and systemic sclerosis progression.”    

Help support cutting-edge research by making a donation today!


 
ANRF
Article Author
Arthritis National Research Foundation
arthritisresearch@curearthritis.org

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

No Comments

Post A Comment