What is your current area of rare disease research?
We study a rare disease called tuberous sclerosis complex (TSC). TSC causes tumors to form in several major organs including the heart, brain, lungs, kidneys, and skin. These tumors, especially the brain tumors, can have serious clinical implications such as infantile spasms, epilepsy, autism, and cognitive delays. TSC is estimated to afflict 50,000 individuals in the U.S.

Why are you studying rare diseases? What got you interested in this field?
During my postdoctoral training at Harvard, I studied under John Blenis, an expert cell biologist with extensive knowledge in the PI3K/mTOR pathway. I came to learn about TSC during this time, because the disease is caused by mutations in two tumor suppressor genes, TSC1 and TSC2, which reside within the mTOR pathway. What really drove me to study TSC, however, was my interactions with TSC patients and their family members. Seeing the pediatric patients suffer from debilitating seizures, and the impact this has on their parents and siblings – this really motivates me to uncover the biological complexities of the disease. Further, the broad spectrum of symptoms and disease is quite remarkable. Some patients have no symptoms and may live most of their lives undiagnosed; while more severely affected patients can suffer from numerous seizures each day. Ultimately, we hope that our research in the lab will contribute to new, future therapies for TSC patients.

What do you wish people knew or understood about rare disease research?
Rare disease research faces many challenges. In the current research climate, scientists face stiff competition for research dollars in all areas of biomedical research; but for rare diseases, there is even less funding available. For many rare diseases, like TSC, there is no cure and more research is desperately needed. Awareness, understanding, and support are essential for rare disease patients and future research.

What have you learned from the rare disease community?
The TSC community, and broader rare disease community, has amazed me over the past several years through their support of each other, commitment to research, and optimism for improved therapies. These patients and their families have inspired me to never, ever, give up!

Learn more about Dr. MacKeigan’s research here.

What is your current area of rare disease research?
Potential metabolic causes of congenital birth defects as well as genetic causes of rare diseases.

Why are you studying rare diseases? What got you interested in this field?
I have always been interested in how humans develop from a single cell into a human being. I began my career as an OB/GYN where I was able to learn some about fetal development, but I realized I wanted to study the genetic mechanisms of development, so went back for training in medical genetics. I have now been practicing medical genetics for eight years here in Grand Rapids.

What do you wish people knew or understood about rare disease research?
It is extremely complex, takes funding which can be hard to acquire, and can take a lot of time. It is an underserved area in the medical community.

What have you learned from the rare disease community?
Patients and their families are tremendously resilient and want any answers they can receive. They are incredibly willing to participate in research in any way they can so that even if they can’t find answers or treatment for their loved ones, perhaps they can help someone else in the future.

See more of Dr. Mark’s research and publications here.

What is your current area of rare disease research?
Cell and Molecular Basis of Neurodegeneration in Multiple System Atrophy.

Why are you studying rare diseases? What got you interested in this field?
I want my lab to include projects that will ultimately help people who have limited medical alternatives.

I was recruited into studying MSA after an article about my lab’s genomics methods-based research appeared in the Wall Street Journal. A man, whose wife was an MSA patient, and her neurologist convinced me to apply those methods to samples from MSA patients.

What do you wish people knew or understood about rare disease research?
Rare diseases like MSA have both genetic and environmental underpinnings. A person may carry a genetic variant that causes a rare disease, but might not come down with the illness if environmental triggers are avoided. For example, many genetic variants for neurodegenerative diseases, but might not come down with the problem if exposure to pesticides and/or industrial chemicals can be avoided.

What have you learned from the rare disease community?
Over the years, I have met many incredible MSA patients and their caregivers who are absolutely dedicated to helping other patients understand how to deal with the heartbreaking problems associated with MSA. These selfless individuals have also spent much time raising MSA awareness across the country to help influence government agencies and foundations to support research aimed at helping find a cure for MSA.

What is your area of research?
We study challenging variants known as Variants of Uncertain Significance or VUS. Rare disease genetics discover rare variants, most times variants no one has ever studied or seen. Our goal is to bring insights to each one of these variants over the broad spectrum of rare diseases. This requires the development of tools to understand both how a gene alters human biology and how the variant alters the gene. To do this we utilize computational tools to generate hypotheses, followed by testing these hypotheses with additional tools ranging from biochemistry to the use of induced pluripotent stem cells and human organoids. More recently we have been trying to understand how to use RNA to gain insights into how DNA changes give rise to rare diseases within cells, including the recent discovery of Viral Induced Genetics. The ultimate goal of our work is to bring research opportunities to every variant where there is a need for better understanding.

Why are you studying rare diseases? What got you interested in this field?
The team of Nic Volker, Howard Jacob, and Elizabeth Worthey. I finish my PhD right after the first successful case of whole-exome sequencing within Nic Volker by the Jacob and Worthey labs at the Medical College of Wisconsin (MCW). I knew this was what I wanted to do, help kids by exploring the details of the genome. So I joined the Jacob lab, working with many of the world leaders in rare disease genomics. Over six years of training with the Jacob lab, which spanned time at MCW and HudsonAlpha, my passion for bringing research to the most challenging genomic variants continued to grow, especially seeing how devastating VUS could be for families and clinicians. In 2018, I was given the opportunity to come to Grand Rapids with Michigan State University and partner our tools with Spectrum Health and Helen DeVos Children's Hospital.

What do you wish people knew or understood about rare disease research?
Sequencing a genome is easy. Understanding what the genome says is now the hardest part. We need continued support, community engagement, and research leaders to invest into understanding more of what the genome encodes. Having a broader knowledge of the proteins coded by the genome makes rapid analysis of variants possible. This is advanced when families, patients, and clinicians unite to bring our genomics understanding into a world initiative, linking others with similar variants.

What have you learned from the rare disease community?
Our research matters, but we need to constantly keep our eyes on the clinical aspects of what we do and morph our research as needed. My eyes were opened on one of the first VUS I was asked to help on back in 2014 at MCW. Three days into helping on a variant, I was informed that the patient passed away. I knew how I viewed genetic variant research needed to change, we needed to do work in a timeframe that helps families instead of helping only basic knowledge that goes through an iterative slow research methodology. For most researchers, our timelines are those of research, meaning that taking on a project means months of work. But clinical requires answers quicker. This became a huge part of morphing our groups computer and data strategies, to get answers as quick as possible.

To learn more about Dr. Prokop’s work visit his website or read about his research.