The MacKeigan Lab uses tumor biology and molecular pathway knowledge to study tuberous sclerosis complex, or TSC. TSC is a rare disease, characterized by mutations in TSC1 or TSC2, two tumor suppressor genes located in the mTOR pathway. Often diagnosed during childhood, the disease causes benign tumors in major organs including the brain, kidneys, skin, and heart. Although non-cancerous, these tumors can result in serious health issues such as epilepsy, autism, and renal failure. The Tuberous Sclerosis Alliance estimates that approximately 50,000 Americans suffer from this disease. There is no cure.
Current therapies for TSC patients involve invasive surgical resection or treatment with rapamycin analogues (everolimus or sirolimus). While these drugs are effective at regressing tumors, patients are required to take the medication long term, which is not ideal given the drugs’ immunosuppressive properties. Also worth noting, once rapamycin treatment ends, patients relapse with problematic tumors. New, more effective treatments are needed for severely afflicted TSC patients suffering from daily seizures and life-threatening disease complications. Our Pathway of Hope project aims to make research discoveries that will ultimately lead to new therapeutic options for TSC. We are approaching the disease from multiple angles.
The MacKeigan Lab has expertise in chemical screening technologies, and is using patient cell lines to identify compounds that decrease TSC cell viability. These novel compounds will be validated in additional biochemical assays, and will ultimately be tested in relevant preclinical models for therapeutic efficacy.
Our team has sequenced multiple TSC biospecimens in search of genomic aberrations. With the help of bioinformatics and epigenetic experts, we are analyzing the results and characterizing the genomic landscape of TSC. This study will identify genetic similarities among TSC patients, which could be targeted for future therapeutic development.
The lab is working with clinicians at Cincinnati Children’s Hospital Medical Center to conduct a collaborative clinical study. This research will address a current gap in knowledge by investigating whether individual genomic analysis can inform clinical decision-making and predict patient outcomes.
TSC researchers have few options when it comes to preclinical models of the disease. We are validating current models used in the field, piloting less common model designs, and working to develop novel models. Accurate, timely preclinical models are essential for gaining biological insights and testing new therapies for TSC.
The MacKeigan Lab feels extraordinarily humbled through our interactions with TSC patients, families, and clinicians. The TSC community is passionately committed to combatting this disease, and we are honored to participate in this research field, and hopeful that we will make impactful contributions.
Jeffrey MacKeigan, Ph.D.
Principal Investigator, Van Andel Institute
Darcy Krueger, M.D., Ph.D.
Co-investigator, Cincinnati Children’s Hospital Medical Center
Hui Shen, Ph.D.
Collaborator, Van Andel Institute
Hope Northrup, M.D.
Collaborator, University of Texas Houston
Katie Martin, Ph.D.
Scientific Project Leader, Van Andel Institute
Kellie Sisson, B.S.
Research Associate, Van Andel Institute
Nicole Doppel, B.S.
Research Department Administrator
Peter Laird, Ph.D.
Van Andel Institute
Len Post, Ph.D.
BioMarin Pharmaceuticals, Inc.
National Organization for Rare Disorders
We are grateful for the generous funding provided by our project sponsors and donors. Our research would not be possible without your support!
MEDC/State of Michigan
Van Andel Institute
Blue Cross Blue Shield of Michigan Foundation
Charlie and Pam Brickey
Great Lakes Scrip Center