Description of Research Expertise

My expertise is in rare disorders that affect LDL and HDL cholesterol metabolism. My research interest is focused in understanding the cause of these conditions, finding novel ways to treat them, and ultimately improve their clinical management. 

Currently, I have two active areas of research in rare disorders affecting LDL and HDL metabolism:

Homozygous Familial Hypercholesterolemia or HoFH - HoFH is the rarest form of Familial Hypercholesterolemia (FH) and affects approximately 1 in every ~350,000 people. Untreated LDL cholesterol levels are usually >400 mg/dL, and if left untreated, are associated with premature cardiovascular disease as early as childhood. Patients with HoFH respond insufficiently to conventional lipid lowering drugs, such statins. Penn has a longstanding research program dedicated to the development of novel treatment options for HoFH, spanning from gene therapy to the development of lomitapide and, more recently, evinacumab.

LCAT deficiency – Lecithin:cholesterol acyl transferase (LCAT) is an enzyme involved in cholesterol metabolism. It esterifies the cholesterol carried by HDL and LDL. Familial LCAT deficiency (FLD) and fish-eye disease (FED) are two very rare disorders caused by LCAT deficiency. Both disorders are associated with very low HDL levels and corneal opacities. Additionally, patients with FLD develop renal disease early in life that often quickly progresses to renal failure requiring dialysis or transplant.
If you would like to learn more about these diseases or are interested in collaborating in my research, you can contact me at: mcuchel@pennmedicine.upenn.edu.

Ongoing Clinical Research Programs:
CASCADE FH Registry (NCT01960244): A longitudinal observational registry for patients diagnosed with FH.
HICC registry (NCT04815005): An international registry specifically dedicated to collecting data on HoFH.
LCAT-D registry (NCT06217588): An international registry specifically dedicated to collecting data on LCAT deficiency.