Genevieve Crane, MD, PhD

When Ribosomes Go Rogue: Investigating a Rare Disorder To Transform Cancer Care

Every cancer deserves attention, even the rarest ones. That’s one of the reasons a dedicated team of researchers at Cleveland Clinic is turning their focus to a lesser-known condition: Cartilage Hair Hypoplasia (CHH).

CHH is a rare genetic disorder that affects an underserved group in our community. It’s characterized by short-limb dwarfism, sparse hair, immune system challenges, anemia and an increased risk of certain cancers, particularly basal cell carcinoma and non-Hodgkin lymphoma, even in children and young adults.

Physician-scientists Genevieve Crane, MD, PhD, Seth Corey, MD, MPH, and Rabi Hanna, MD, have teamed up to better grasp CHH and the patients who live with it. Ribosomes, which are essential parts of cells responsible for building proteins, are not generated properly in this patient population. This dysfunction may play a role in cancer risk.

“The ribosome provides a therapeutic vulnerability that has not been exploited yet by cancer therapy,” says Dr. Corey. “We’re using this as a model system to better understand how the host, environment, immune system and viral exposures interact.”

By studying blood samples from patients with CHH and comparing them to healthy siblings or age-matched controls, Dr. Crane, Dr. Corey and Dr. Hanna hope to uncover new insights into this understudied group of patients. They are investigating how these ribosomes are being made and how that process may differ from normal.

“We’re thinking about how we can understand this better to help kids who have abnormal ribosome generation and an abnormal immune response,” says Dr. Crane. “Some of these kiddos have very severe immune deficiency and ultimately need a bone marrow transplant to address that.”

Additionally, some of the changes may help protect patients with CHH from developing certain types of lymphoma, despite their elevated risk due to compromised immune function. A deeper understanding of how these patients’ cells are affected could not only support efforts to enhance immune function in CHH but also provide insights that may be leveraged for cancer treatment.

Initiatives like VeloSano make it possible for researchers to pursue bold questions and explore rare conditions like CHH. This team especially knows how vital community support is in transforming scientific ideas into lifesaving care.

“Cancer doesn’t only affect the patient,” says Dr. Hanna. “It affects the whole family, and it affects the whole community. VeloSano is a way for the community to come together to help find a cure or even an improvement to a cure, and we depend on the generosity of the community.”