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The Pathway of Hope

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.

PathwayofHope_goals

 

Cell screen for new drug targets

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. 

Genomic profiling individual tumors

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.

PATHWAYOFHOPE_TSCgenomiclandscape

Precision medicine clinical study

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.

Preclinical modeling and validation

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.

Pathway of Hope Team 

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 

Advisory Board

Peter Laird, Ph.D.
Van Andel Institute

Len Post, Ph.D.
BioMarin Pharmaceuticals, Inc.

Peter Saltonstall
National Organization for Rare Disorders

Sponsors and Donors 

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
Colliers International
Rockford Construction
Team Hannah