Welcome to the Sime Lab

Sime Lab GroupWelcome to the Sime Laboratory. We invite you to learn more about us from this web site and please feel free to contact us anytime. We would be pleased to hear from you.

Our laboratory focuses on identifying pathogenetic mechanisms underlying lung disease so that we can speed the identification and development of new and exciting therapeutics. Diseases we study include lung scarring (fibrosis) and smoke and other toxicant induced lung inflammatory diseases such as chronic bronchitis and emphysema (COPD).

Our laboratory studies are translational in nature with our work bridging in vitro studies to in vivo models of human disease and patient studies. We have also been involved in both investigator-initiated and pharma sponsored clinical trials, and are fortunate to have been funded continuously by the NIH as well as Department of Defense, the American Lung Association, industry and philanthropy. 

An important mission of the lab is to help train the next generation of basic, translational and clinical researchers. We are fortunate to collaborate widely across the institution, nationally and internationally and have a team-based approach to problem solving. Our trainees have been supported by NIH training grants including NIH T32s, F and K awards and are enjoying successful careers in academia, industry and government. Our trainees include graduate students, clinical fellows and post-doctoral fellows. All are welcome!

The Sime Lab is currently looking for graduate students, post-docs and fellows with an interest in our research. For more information contact Dr. Sime.

Mechanisms of Pulmonary Fibrosis

Sime Lab imageFibrosis (also called scarring) is estimated to be important in about 45% of human deaths. It is the result of a dysregulated uncontrolled wound healing response. When scarring occurs in vital organs the results can be devastating. Pulmonary fibrosis is a progressive disease with a shorter survival time than lung cancer. Patients with lung scarring develop shortness of breath, cough, disability and sadly sometimes succumb to these disorders. Fibrosis can occur without an identifying cause (idiopathic pulmonary fibrosis) or can be the result of dust inhalation, irradiation, exposure to toxicants and drugs and can occur with autoimmune diseases such as rheumatoid arthritis and systemic sclerosis.

Our laboratory is NIH and industry funded to investigate the mechanisms of lung fibrosis. Specifically, we are interested in the role of matrix (the stiff glue of the scar tissue and especially cross-linking enzymes called tissue transglutaminases), abnormal metabolism (glycolysis) in cells within the lung and aspects of biomechanical tissue stiffness and stretch. To address these different aspects of fibrosis we have available primary human cells, in vivo models of disease and patient samples. We utilize cellular, genetic, lipidomic and metabolomic and physiologic approaches to interrogate pathways and collaborate with experts in big data and machine learning approaches to assist in some of the complex analyses.

Lung Inflammation and Resolution

Sime Lab imageInflammation occurs in organs following an insult and underpins much of human disease including lung diseases such as asthma, chronic obstructive pulmonary disease (COPD, chronic bronchitis and emphysema), cystic fibrosis, and some aspects of lung cancer. While we know much of the pro-inflammatory pathways that drive disease, our understanding of the resolution of inflammation is much less well understood. This is important as speeding resolution is likely an important new therapeutic option. In the last few years we have some to understand that resolution of inflammation is an active process. It requires complex cellular interactions and production of distinct mediators. Some of these mediators are derived from omega 3 and 6 fatty acids and include resolvins, protectins and maresins. We are examining how these mediators and pathways may be abnormal in patients with COPD and other lung diseases, and hypothesize that these SPMs may be exciting therapeutics for inflammatory disease. Further, we are very interested in understanding the complex interplay between lung infections, inflammation and resolution as many patients with lung disease develop infective exacerbations of their disease leading to morbidity, impaired quality of life, hospitalizations and economic costs. We use patient and control primary cells, in vivo models, pathologic assessments, physiologic measurements and state of the art lipidomics, cell biology and genetics to address our hypotheses.

Our research will allow us to understand why people who smoke suffer persistent lung damage even after quitting, and to understand why smokers and ex-smokers are at increased risk of lung infection. We will also study new potential therapies to repair lung damage and restore normal immune responses. Our long-term goal is to design therapies that, in combination with quitting smoking, will improve health and reduce disease in former smokers and people exposed to second-hand and environmental smoke from other sources (Biomass and Burn Pits).

 

About Dr. Patricia J. Sime

VCUSOM About Dr. Patricia J. Sime

About Dr. Patricia J. Sime

Dr. Sime is a physician scientist who received her M.D. training at the University of Edinburgh, Scotland, where she graduated with honors. She pursued her training in pulmonary medicine in Edinburgh before traveling to McMaster University, Ontario, Canada, to train in the science of inflammatory and scarring lung diseases. In 1999, she was recruited to the faculty at the University of Rochester Medical Center (URMC) as a physician, educator and researcher. During her term at URMC, she held the position as Vice Chair for Research and was the Chief of the Pulmonary and Critical Care Division in the Department of Medicine. She was also director of the Interstitial Lung Disease Clinic and built a translational research program focused on lung fibrosis and inflammation. Dr. Sime has received numerous awards for mentorship and scientific achievement. She has published more than 150 manuscripts, holds patents, has served as a standing member of an NIH study section and contributed to journal editorial boards.

In July 2019 she assumed the position as Chair of the Department of Internal Medicine at VCU. Dr. Sime holds the William Branch Porter Distinguished Professor of Medicine. Her goals are to continue to develop innovative and impactful research and education across Divisions and Departments while helping to support the next generation of researchers, educators and clinicians. Dr. Sime enjoys building research programs across divisions and departments and has a network of outstanding collaborators locally, nationally and internationally.

Learn more about Dr. Patricia J. Sime

Thomas Thatcher, PhD

Thomas Thatcher, PhD

Assistant Professor

Thomas Thatcher, PhD

Thomas Thatcher, PhD

Assistant Professor

Internal Medicine

Education: PhD in Immunology, University of Rochester (2000)

Research Interests: lung inflammation and resolution

Email: thomas.thatcher@vcuhealth.org

View Faculty Expertise Profile

Maggie Thomas Freeberg, PhD

Maggie Thomas Freeberg, PhD

Post-doctoral Research Fellow

Maggie Thomas Freeberg, PhD

Maggie Thomas Freeberg, PhD

Post-doctoral Research Fellow

Internal Medicine

Education: PhD and MS in Biomedical Engineering, University of Rochester, BS in Biomedical Engineering, University of Minnesota

Research Interest: Mechanotransduction mechanisms leading to pulmonary fibrosis progression

Outside Lab Interests: Outdoor adventure (hiking, kayaking, rafting, etc), cooking, board games, dogs, craft beer

Email: margaret.freeberg@vcuhealth.org

Jane Rebman, PhD

Jane Rebman, PhD

Senior Lab Technician

Jane Rebman, PhD

Jane Rebman, PhD

Senior Lab Technician

Internal Medicine

Education: PhD in Integrative Life Sciences, Virginia Commonwealth University, BS in Biology, Virginia Commonwealth University

Outside Lab Interests: Crafting (crocheting and quilting/sewing), running, spending time with family, avid white wine enthusiast

Email: jane.rebman@vcuhealth.org

Rachel Oppelt

Rachel Oppelt

Senior Administrative Coordinator for Dr. Sime

Rachel Oppelt

Rachel Oppelt

Senior Administrative Coordinator for Dr. Sime

Internal Medicine

Rachel has been supporting Dr. Sime administratively since February 2017. She graduated with an Associates in Applied Science Degree from Genesee Community College in 2017. Rachel has an extensive background in administration and supported Dr. Sime back in Rochester, NY.

Outside Lab Interests: In her free time, she enjoys being outdoors and traveling back home to see her family when she’s able.

Email: rachel.oppelt@vcuhealth.org

Alumni

PFF logoThe Sime Lab has ongoing collaborations with other research teams around the world and in Virginia, including George Mason University and Fairfax Inova Hospital. Our funding sources include the National Institutes of Health, Industry, Philanthropy and Private Foundations. We gratefully acknowledge the support and friendship of the Pulmonary Fibrosis Foundation and our patients and their families, who make our research meaningful.