Lupus, Latin for “wolf,” is an insidious disease, aptly named for the way that ravenous creature devours its target.
Lupus, or systemic lupus erythematosus, is a progressive, degenerative disease in which the immune system turns against itself, attacking a person’s healthy tissue, cells and organs. Confounding doctors and devastating sufferers, the symptoms can range from debilitating pain and fatigue to organ failure and a host of other impairments. The Lupus Foundation of America estimates 1.5 million Americans, and at least five million people worldwide, have a form of lupus. Although there is no cure, a new researcher at the University of Houston thinks there could be one in the future, and he is on a quest to find it.
Starting out as a physician, Dr. Chandra Mohan found a majority of the patients in his rheumatology practice had lupus. He was always asked, “Is there a cure?” Although the answer is, “no,” Mohan couldn’t help thinking, “Why not?” From there, a second career was born, and he decided to get behind the microscope.
Mohan, who has an M.D. in pathology and rheumatology and a Ph.D. in cellular immunology, joined UH in 2013 as the Hugh Roy and Lillie Cranz Cullen Distinguished University Professor in biomedical engineering. He and his research group moved here from UT Southwestern in Dallas. He says a number of people reached out to him about the opportunities Houston and UH have to offer that would give him the chance to expand his health-oriented research.
“This tells us we can no longer think of a disease as a single entity. We must consider the entire landscape of molecules as changing in a given patient. ”
“One thing I found very attractive is that UH is in the middle of the Texas Medical Center (TMC), so there is tremendous access to patients and patient materials,” Mohan says. “Another motivation was that Houston is a hub for technology. So many institutions are engaged in cutting-edge research and in developing new technologies for diagnostics and therapeutics. I’m glad I came here. We have many collaborations with TMC physicians, not only in the area of lupus, but also other diseases.”
While lupus is of primary interest, his lab also is investigating related rheumatic autoimmune diseases, such as rheumatoid arthritis and systemic sclerosis. According to the National Institutes of Health, there are more than 100 rheumatic diseases afflicting more than 46 million people in the U.S. Specifically, Mohan’s team is working to understand both their genetic and non-genetic origins.
Launching an Attack Against Itself
As with lupus, these illnesses occur when a person’s immune system, which normally generates antibodies to defend the body from invading organisms, turns to launch an attack against itself. In rheumatoid arthritis, an inflammatory disease causing pain, swelling, stiffness and loss of function in the joints, a person’s antibodies wage battle on the membranes lining the joints. In systemic sclerosis, often better known as scleroderma, the skin and lungs are affected, with the skin becoming very tight and a similar sort of pathology taking place in the lungs, making it difficult to breathe.
Seeking new ways to diagnose and manage chronic disease, Mohan and his colleagues are investigating which cells cause these diseases and which are the culprit genes. Over the years, however, he has found the triggers that activate many diseases are partly genetic and partly non-genetic, so he has expanded his research to consider both.
“We’re also very interested in understanding non-genetic factors that may contribute to rheumatic disease,” Mohan says. “ This could include the food we eat, environmental chemicals, sunlight exposure and infections. Most of these factors are very poorly understood or studied. The second important aspect is management. Once patients are diagnosed, how do we monitor and treat them?”
Much of his lab ’s work is invested in identifying new biological indicators of disease, called biomarkers, that could predict which patient will fare better and which will fare worse. Since most of this boils down to protein biomarkers, his team has established technologies that interrogate levels of large numbers of proteins to identify the few that may be predictive of who is going to develop what over time. Biomarker studies are also of interest therapeutically, he says, because some are good therapeutic targets. Once biomarkers that can predict disease progression are identified, the next step will be to test those particular proteins as therapeutic targets. While most targets would require antibody or molecule inhibitors, Mohan is also interested in trying out natural therapies that may potentially have fewer side effects.
Entire Landscape of Genes
“An important technological change is that we now can study biomarkers in a global fashion, whereas we previously were limited to studying one gene at a time,” he explains. “But now we can look at the entire landscape of genes in the body. This is called genomics. Likewise, we now can engage in proteomics and metabolomics, which mean studying proteins and metabolites globally, instead of just one at a time, as was the case in the not-too-distant past.”
Mohan’s lab is active in applying proteomic and metabolomic approaches to rheumatic disease. This gives them a global snapshot of all the molecules in a given person and disease and has led to another important change in their understanding of chronic illnesses.
“There’s a lot of overlap in what activates different diseases, with several common themes among them,” Mohan says. “For instance, in a study we did on lupus patients that revealed findings quite different from what we see in people who have other rheumatic diseases, we found that lupus seems to be quite striking in its metabolic changes. Those with lupus had a large faction of metabolomes shared with those who have metabolic syndrome, diabetes, chronic renal disease and some cancers. This tells us we can no longer think of a disease as a single entity. We must consider the entire landscape of molecules as changing in a given patient, as well as realize that people often have multiple conditions coexisting at the same time.”
Findings such as these led Mohan to the realization that it’s important to think in a holistic fashion, leading him to cast a wider net and expand his research to other diseases.
“ These same approaches could be very useful in investigating other chronic diseases, such as diabetes, hypertension and cardiac disease,” Mohan says. “We’ve been successful in setting up technologies to systematically examine different body fluids of potential biomarkers. Since the technologies are working so well, we thought we should apply them to as many chronic conditions as we could get our hands on, because it could make a difference in how they are managed. We have collaborations with the Texas Medical Center, so it takes us beyond rheumatic disease.”
Other researchers closely collaborating with him are Tianfu Wu, an assistant professor of biomedical engineering, specializing in biomarker discovery and therapeutic interventions for autoimmune diseases; Research Assistant Professor Yong Du, a nephrologist with an M.D. and Ph.D., specializing in kidney disease; and research associate Simanta Pathak. Rounding out the team are research technicians Kamala Vanarsa and Sneha Ravikumar, as well as a mix of post-baccalaureate, graduate and post-doctoral students, and clinical fellows.
A Taste of Medical School
Mohan is excited to be the inaugural instructor of a new class called “Introduction to Diseases.” The course is designed to bring a taste of medical school to the undergraduate level and will be critical to students planning careers in health care. Furthering the mission of UH Health, Mohan hopes it will inspire the younger generation to focus on what ’s important in health and health care and better understand the needs of society.
“The future is very bright for health-oriented research, not just in my lab, but in any lab in Houston,” Mohan says. “We’re definitely in the right place at the right time in Houston.”