Ami K. Mankodi, M.D.
Hereditary Muscle Diseases
Building 35, Room 2A-1002
35 Convent Drive
Bethesda, MD 20892-3075
The goals of our research are to explore disease mechanisms in hereditary adult-onset skeletal muscle diseases with a focus on identifying targets for treatment and characterizing outcome measures in preparation for drug therapies.
Currently, our laboratory group is focused on distal myopathies caused by myofibrillar myopathies which are a rare inherited degenerative skeletal muscle diseases characterized by myofibrillar dissolution and abnormal accumulation of degraded myofibrillar proteins. Despite a high proportion of undiagnosed affected individuals, at least 9 genes have successfully been identified. Our group has recently discovered that some mutations in LDB3 reside in a region that directly interacts with skeletal muscle actin filaments and causes the disruption of actin cytoskeleton in a splice-isoform specific manner in transfected mouse skeletal muscle cells and in electroporated tibialis anterior muscle fibers of adult mice. Through national and international collaborations, we are now uncovering the structure of the LDB3 and skeletal muscle actin interaction using cryo-electron microscopy and x-ray crystallography. We are developing mouse models of myofibrillary myopathy, which would be important tools in our understanding of underlying disease mechanisms, in identifying targets for treatment and in screening for novel drug therapies.
Our clinical team is focused on a rare degenerative multisystem disorders with heterogeneous clinical manifestations – myotonic dystrophy (DM). Muscles in the distal leg, hand and forearm are affected early and prominently in DM type 1. Our group has a keen interest in identifying tools to measure the hand and distal leg function particularly in regards to the effects of myotonia and weakness. We are also developing clinical and imaging biomarkers of pulmonary function in DM1 patients including assessment of diaphragm and intercostal muscles. Through the Myotonic Dystrophy Collaborative Research Network (DMCRN) and NIH initiated clinical studies, we are characterizing clinical endpoints, imaging and molecular biomarkers of disease progression, disease mechanism and therapeutic response in DM patients.
Grunseich C, Sarkar N, Lu J, Owen M, Schindler A, Calabresi PA, Sumner CJ, Roda RH, Chaudhury V, Lloyd TE, Crawford TO, Subramony SH, Oh SJ, Richardson P, Tanji K, Kwan JY, Fischbeck KH, Mankodi A. Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases. J Neurol Neurosurg Psychiatry. 2021.
Pathak P, Blech-Hermoni Y, Subedi K, Mpamugo J, Obeng-Nyarko C, Ohman R, Molloy I, Kates M, Hale J, Stauffer S, Sharan SK, Mankodi A. Myopathy associated LDB3 mutation causes Z-disc disassembly and protein aggregation through PKCα and TSC2-mTOR downregulation. Commun Biol. 2021;4(1):355.
Liu CY, Yao J, Kovacs WC, Shrader JA, Joe G, Ouwerkerk R, Mankodi AK, Gahl WA, Summers RM, Carrillo N. Skeletal Muscle Magnetic Resonance Biomarkers in GNE Myopathy. Neurology. 2021;96(5):e798-e808.
Gaur L, Hanna A, Bandettini WP, Fischbeck KH, Arai AE, Mankodi A. Upper arm and cardiac magnetic resonance imaging in Duchenne muscular dystrophy. Ann Clin Transl Neurol. 2016;3(12):948-955.
Mankodi A, Kovacs W, Norato G, Hsieh N, Bandettini WP, Bishop CA, Shimellis H, Newbould RD, Kim E, Fischbeck KH, Arai AE, Yao J. Respiratory magnetic resonance imaging biomarkers in Duchenne muscular dystrophy. Ann Clin Transl Neurol. 2017;4(9):655-662.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on August 17th, 2021