Dirk Hubmacher, PhD

Dr. Hubmacher received his Ph.D. from the University of Lübeck in Germany in 2004 and entered the field of extracellular matrix biology as a postdoctoral fellow with Dr. Dieter Reinhardt (McGill University, Montreal) to study mechanisms of fibrillin microfibril formation and their pathogenic modification with homocysteine. In 2011, he moved to the laboratory of Dr. Suneel Apte at the Cleveland Clinic Lerner Research Institute to study the function of ADAMTS proteases and ADAMTS-like proteins in mouse models of human genetic disorders. During his postdoctoral training in Dr. Reinhardt’s laboratory, he discovered that fibrillin microfibrils are altered by homocysteine and that these alterations had similar molecular consequences as point mutations in fibrillin-1 causing Marfan syndrome, thus providing a potential explanation for the phenotypic overlap of homocystinuria and Marfan syndrome. In addition, he described a novel mechanism for the assembly of fibrillin microfibrils that involves the multimerization of the C-terminal end of the fibrillin molecule. In Dr. Apte’s laboratory, he found that aspects of the lung phenotype in ADAMTSL2 knock-out mice resemble tissue biopsies from geleophysic dysplasia patients and he linked these to alterations in fibrillin-2 microfibril formation. In several studies, he contributed novel insights into the formation and maintenance of the ciliary zonule in the eye, contributing to the understanding of the development of this structure and suggesting pathological mechanisms for lens dislocation (ectopia lentis), a hallmark feature of Marfan syndrome and associated disorders. 

 

Dr. Hubmacher’s current research continues to focuses on the role of ADAMTS proteases and ADAMTS-like proteins, in conjunction with fibrillin microfibrils, in the formation of musculoskeletal tissues. The musculoskeletal disorders caused by mutations in the respective proteins are characterized by severe short stature, short hands and feet, stiff joints, and a pseudomuscular built. To elucidate the biological role of ADAMTS proteases and ADAMTS-like proteins, Dr. Hubmacher’s laboratory has generated mouse models of these disorders and uses cell-based assays and biochemical and biophysical approaches to dissect hierarchical protein-protein interactions in the extracellular matrix and to determine responses of tissue-resident cells to faulty extracellular matrices deposited in disease conditions. The work of Dr. Hubmacher is currently funded by an RO1 grant from the NIH (NIAMS) and was previously recognized by a postdoctoral fellowship from the German Academic Exchange Service, a Young Investigator Award from the Marfan Foundation, and an Early Investigator Grant from the Marfan Foundation.

Web site: http://labs.icahn.mssm.edu/hubmacherlab/