David Goldhamer

Professor

Molecular and Cell Biology / Cell and Developmental Biology

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Education: Ph.D. Ohio State University, Postdoctoral study, University of Virginia and Fox Chase Cancer Center

Research Interests: We use basic and translational approaches in the mouse to investigate the development, regeneration and repair of the musculoskeletal system.  A key component of our research program is the use of genome modification technologies to understand fundamental cell biological processes at the genetic and molecular levels.  Current areas of interest include the following:

• Regulatory circuitry controlling muscle-resident stem cell programming and differentiation in regenerating muscle and in muscular dystrophies
• Stem cell therapeutics for repair of muscle and bone
• Embryological origins of muscle stem cells
• Pathophysiology of heterotopic ossification, with a focus on the early initiating events following injury and in fibrodysplasia ossificans progressiva (FOP)
• Muscle-bone interactions in early development
• Transcriptional regulation of muscle regulatory genes in muscle development and regeneration

Selected Publications:

Burdick, L. N., DelVichio, A. H., Hanson, L. R., Griffith, B. B., Bouchard, K. R., Hunter, J. W., and Goldhamer, D. J. (2024). Sex as a critical variable in basic and pre-clinical studies of fibrodysplasia ossificans progressiva. Biomolecules 14, 177. https://doi.org/10.3390/biom14020177

 Yamamoto, M., Stoessel, S. J., Yamamoto, S., and Goldhamer, D. J. (2022). Over-expression of wild-type ACVR1 in fibrodysplasia ossificans progressiva mice rescues perinatal lethality and inhibits heterotopic ossification. J. Bone Miner. Res. https://doi.org/10.1002/jbmr.4617.

Lees-Shepard, J. B*., Stoessel, S. J.*, Chandler, J., Bouchard, K., Bento, P., Apuzzo, L. N., Devarakonda, P. M., Hunter, J. W., Goldhamer, D. J. (2022). An anti-ACVR1 antibody exacerbates heterotopic ossification by fibro-adipogenic progenitors in fibrodysplasia ossificans progressiva mice. J. Clin. Invest. 132(12):e153795. https://doi.org/10.1172/JCI153795.  *co-first authors

Yagi, M., Ji, F., Charlton J., Cristea S., Messemer, K., Horwitz, N., Di Stefano, B., Tsopoulidis N., Hoetker, M., Huebner, A., Almada A., Yamamoto, M., Patelunas A., Goldhamer, D. J., Wagers, A., Michor, F., Meissner, A., Sadreyev, R., and Hochedlinger, K. (2021). Dissecting dual roles of MyoD during lineage conversion to mature myocytes and myogenic stem cells. Genes & Development 35, 1-20.

Wood, W. M., Otis, C., Etemad, S., and Goldhamer, D. J. (2020). Development and patterning of rib primordia are dependent on associated musculature. Dev. Biol. 468, 133-145.

Fortin, J., Tian, R., Zarrabi, I., Hill, G., Williams, E., Sanchez-Duffhues, G., Thorikay, M., Ramachandran, P., Siddaway, R., Wong, J. F., Wu,  A., Apuzzo, L. N., Haight, J., You-Ten, A., Snow, B., Wakeham, A., Goldhamer, D. J., Schramek, D., Bullock, A. N., Dijke, P. T., Hawkins, C., and Mak, T. W.^. (2020). Mutant ACVR1 arrests glial cell differentiation to drive tumorigenesis in pediatric gliomas. Cancer Cell 37, 308-323. e12

Joseph, G. A., Hung, M., Goel, A. J., Hong, M., Rieder, M-K., Beckmann, N. D., Serasinghe, M. N., Chipuk, J. E., Devarakonda, P. M., Goldhamer, D. J., Aldana-Hernandez, P., Curtis, J., Jacobs, R. L., Krauss, R. S. (2019). Late-onset megaconial myopathy in mice lacking group I Paks. Skeletal Muscle 9, 5.

Goldhamer, D. J. and Lees-Shepard, J. B. (2019). Response to comment on ‘Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity.” eLife 8. doi:10.7554/eLife.43928

Lees-Shepard, J. B., and Goldhamer, D. J. (2018). Stem cells and heterotopic ossification: lessons from animal models. Bone, 109, 178-186.

Lees-Shepard, J.B., Nicholas, S.-A.E., Stoessel, S.J., Devarakonda, P.M., Schneider, M.J., Yamamoto, M., Goldhamer, D.J., 2018. Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity. eLife 7, 305. doi:10.7554/eLife.40814

Yamamoto, M., Legendre, N. P., Biswas, A., Lawton, A., Yamamoto, S., Tajbakhsh, S., Kardon, G., and Goldhamer, D. J. (2018) Loss of MyoD and Myf5 in skeletal muscle stem cells results in altered myogenic programming and failed regeneration. Stem Cell Reports 10, 956-969

Lees-Shepard, J. B., Yamamoto, M., Biswas, A. A., Stoessel, S. J., Nicholas, S-A. E., Cogswell, C. A., Devarakonda, P. M., Schneider Jr., M. J., Cummins, S. M., Legendre, N. P., Yamamoto, S., Kaartinen, V., Hunter, J. W., and Goldhamer, D. J. (2018). Activin-dependent signaling in fibro/adipogenic progenitors causes fibrodysplasia ossificans progressiva, Nature Communications, 9, 471.

Biswas, A., and Goldhamer, D. J. (2016). FACS fractionation and differentiation of skeletal-muscle resident, multipotent Tie2+ progenitors. In, Methods in Molecular Biology (Michael Kyba, editor). Vol 1460, 255-267. Springer Press.

Sierra, A., Subbotina, E., Zhu, Z., Gao, Z., Koganti, S. R. K., Coetzee, W., Goldhamer, D. J., Hodgson-Zingman, D., and Zingman, L. V. (2016). Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin. Biochem. Biophys. Res. Comm. 471, 129-134.

Dey, D., Goldhamer, D. J., and Yu, P. B. (2015). Contribution of Muscle-Resident Progenitor Cells to Homeostasis and Disease. In Molecular Biology of Adult Stem Cells (Ivo Kalajzic, ed). Current Molecular Biology Reports, pp. 1-14.

Nogueira, J. M., Hawrot, K., Sharpe, C., Noble, A., Wood, W. M., Jorge, E. C., Goldhamer, D. J., Kardon, G., and Dietrich, S.  (2015). The emergence of Pax7-expressing muscle stem cells during vertebrate head muscle development.  Front. Aging Neurosci. 7, 1-22.

Zhu, Z, Sierra, A., Burnett, C. M. L., Chen, B., Subbotina, E., Koganti, K., Gao, Z., Wu, Y., Anderson, M. E., Song, L. S., Goldhamer, D. J., Coetzee, W. A.,   Hodgson-Zingman, D. M., Zingman, L. V. (2014). Sarcolemmal ATP-sensitive potassium channels modulate skeletal muscle function under low-intensity workloads. J. Gen. Physiol. 143, 119-134.

McLaughlin, S. W., Wosczyna, M. N., Laurencin, C. T., Goldhamer, D. J.  (2013). “Skeletal Muscle Regenerative Engineering”, In Regenerative Engineering, 1st edition, C. T. Laurencin and Y. Khan, editors. CRC Press/Taylor & Francis Group.

Radzyukevich, T. L., Neumann, J. C., Rindler, T. N., Oshiro, N., Goldhamer, D. J., Lingrel, J. B., and Heiny, J. A. (2013). The Na,K-ATPase α2 isoform in skeletal muscle plays an essential, acute role in exercise performance, contractility, and resistance to fatigue. J. Biol. Chem. 288, 1226-1237.

Martinez, T. L., Kong, L., Wang, X., Osborne, M. A., Crowder, M. E., VanMeerbeke, J. P., Xu, X., Davis, C., Wooley, J., Goldhamer, D. J., Lutz, C. M., Rich, M. M., and Sumner, C. J. (2012). Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy. J. Neuroscience 32, 8703-8715.

Wosczyna, M. N., Biswas, A., Cogswell, C., and Goldhamer, D. J. (2012). Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification. J. Bone Miner. Res. 27, 1004-1017.

Zhang, X., Patel, S., McCarthy, J. J., Rabchevsky, A., Goldhamer, D. J., and Esser, K. A. (2011). A non-canonical E-box within the MyoD core enhancer is necessary for circadian expression in skeletal muscle. Nucl. Acids Res., pp1-12.

Starkey, J. D., Yamamoto, M., Yamamoto S., and Goldhamer, D. J. (2011). Skeletal muscle satellite cells are committed to myogenesis and do not spontaneously adopt non-myogenic fates. J. Histochem. Cytochem. 59, 33-46

Messina, G., Biressi, S., Monteverde, S., Magli, A., Pistocchi, A., Gargioli, C., Campbell, C. E., Tagliafico, E., Grossi, M., Cotelli, F., Goldhamer, D. J., Gronostajski, R. M. and Cossu, G. (2010). NFIX regulates fetal specific transcription in developing skeletal muscle. Cell 140, 554-566.

Alekseev, A. E, Reyes, S., Yamada. S., Hodgson-Zingman, D. M., Sattiraju, S., Zhu, Z., Sierra, A., Gerbin, M., Coetzee, W. A., Goldhamer, D. J., Terzic, A., and Zingman, L. V. (2010). Sarcolemmal ATP-sensitive K+ channels control energy expenditure determining body weight. Cell Metabolism 11, 58-69

Yamamoto, M., Shook, N. A., Kanisicak, O., Yamamoto, S., Wosczyna, M. N., Camp, J. R., and Goldhamer, D. J. (2009). A multifunctional reporter mouse line for Cre- and FLP-dependent lineage analysis. Genesis 47, 107-114.

Lounev, V. Y., Ramachandran, R., Wosczyna, M. N., Yamamoto, M., Maidment, A. D. A., Shore, E. M., Glaser, D. L., Goldhamer, D. J., and Kaplan, F. S. (2009). Identification of progenitor cells that contribute to heterotopic skeletogenesis. J Bone Joint Surg 91: 652-663

Kanisicak, O., Mendez, J. J., Yamamoto, S., Yamamoto, M., and Goldhamer, D. J. (2009). Progenitors of skeletal muscle satellite cells express the muscle determination gene, MyoD. Dev. Biol. 332, 131-141.

Yamamoto, M., Watt, C., Schmidt, R., Kuscuoglu, U., Miesfeld R., and Goldhamer, D. J. (2007). Cloning and characterization of a novel MyoD enhancer binding factor. Mech. Dev. 124, 715-728.

Kirillova,I., Gussoni, E., Goldhamer, D. J., and Yablonka-Reuveni, Z. (2007). Myogenic reprogramming of retina-derived cells following their spontaneous fusion with myotubes. Dev. Biol. 311, 449-463.

O¹Rourke, J. R., Georges, S. A., Seay, H. R., McManus, M. T., Goldhamer, D. J., Tapscott, S. J., Swanson, M. S., and Harfe, B. D. (2007). Dicer is required for embryonic myogenesis. Dev. Biol. 311, 359-368.

Chen, J. C. J., Mortimer, J., Marley, J. and Goldhamer, D. J. (2005). MyoD-cre transgenic mice: a model for conditional mutagenesis and lineage tracing of skeletal muscle. Genesis 41, 116-121.

Chen, J. C. and Goldhamer, D. J. (2004). The core enhancer is essential for the proper timing of MyoD activation in limb buds and branchial arches. Dev. Biol. 265, 502-512.

Chen, J. C. and Goldhamer, D. .J. (2003). Skeletal muscle satellite cells. Reproductive Biology and Endocrinology 1:101.

Andreucci, J. J., Grant, D., Cox, D. M., Tomc, L. K., Prywes, R., Goldhamer, D. J., Rodrigues, N., Bedard, P.-A., and McDermott, J. C. (2002). Composition and function of AP-1 transcriptional complexes during muscle cell differentiation. J. Biol. Chem. 277: 16426-16432.

Chen, J. C., Ramachandran, R., and Goldhamer, D. J. (2002). Essential and redundant functions of the MyoD distal regulatory region revealed by targeted mutagenesis Dev. Biol. 245, 213-223.

Chen, J. C., Love, C. M., and Goldhamer, D. J. (2001). Two upstream enhancers collaborate to regulate the spatial patterning and timing of MyoD transcription during mouse development. Dev. Dyn. 221, 274-288.

Kablar, B., Krastel, K., Ying, C., Tapscott, S. J., Goldhamer, D. J., and Rudnicki, M. A. (1999). Myogenic determination occurs independently in somites and limb buds. Dev. Biol. 206, 219-231.

Kucharczuk, K. L., Love, C. M., Dougherty, N. M., and Goldhamer, D. J. (1999). Fine-scale transgenic mapping of the MyoD core enhancer: MyoD is regulated by distinct but overlapping mechanisms in myotomal and non-myotomal muscle lineages. Development 126, 1957-1965.

Chen, J. C. and Goldhamer, D. J. (1999). Transcriptional mechanisms governing MyoD expression in the mouse. Cell and Tissue Research. (Rolf Zeller, ed.). 296, 213-219.

Kablar, B., Asakura, A., Krastel, K., Ying, C., May, L., Goldhamer, D. J., and Rudnicki, M. A. (1998). MyoD and Myf-5 define the specification of musculature of distinct embryonic origin. Biochem. Cell Biol. 76, 1079-1091.

Kucharczuk, K. L., and Goldhamer, D. J. (1997). Nuclear DNA binding proteins. Methods in Cell Biology (Charles P. Emerson Jr. and H. Lee Sweeney, eds). Vol. 52: 439-472. Academic Press.

Brunk, B. P., Goldhamer, D. J., and Emerson, C. P. Jr. (1996). Regulated demethylation of the myoD distal enhancer during skeletal myogenesis. Dev. Biol. 177, 490-503.

Woloshin, P., Song, K., Degnin, C., McNeil-Killary, A., Goldhamer, D. J., Sassoon, D., and Thayer, M. J. (1995). MSX-1 inhibits expression of MyoD in primary fibroblasts X 10T1/2 cell hybrids. Cell 82, 611-620.

Faerman, A., Goldhamer, D. J., Puzis, R., Emerson, C. P., and Shani, M. (1995). The distal human MyoD enhancer sequences direct unique muscle-specific patterns of lacZ expression during mouse development. Dev. Biol. 171, 27-38.

Goldhamer, D. J., Brunk, B., A. Faerman, A. King, Shani, M., and Emerson, C. P. Jr. (1995). Embryonic activation of the myoD gene is regulated by a highly conserved distal control element Development 121, 637-649.

Litvin, J., Montgomery, M.O., Goldhamer, D.J., Emerson, C.P. Jr., and Bader, D.M. (1993). Identification of DNA binding proteins(s) in the developing heart. Dev. Biol. 156, 409-417.

Goldhamer, D.J., Faerman, A., Shani, M., and Emerson, C.P. Jr. (1992). Regulatory elements that control the lineage specific expression of myoD. Science 256, 538-542.