David J. Glass

David J. Glass (born 1961) is an American biomedical scientist who led Regeneron's skeletal muscle group, before stepping into his more recent role as VP of research, Aging/Age-Related Disorders, at Regeneron Pharmaceuticals.^[1] He also wrote an influential book aimed at teaching biology graduate students how to design their experiments.

David J. Glass
Born	1961 (age 63–64)
Education	Bronx High School of Science, Columbia University (BS), New York Medical College (MD)
Occupation	Biomedical scientist
Employer	Regeneron

Glass is a member of the National Academy of Sciences^[2] and the American Association for the Advancement of Science. Earlier, he was elected to the American Society for Clinical Investigation.^[3] He has more than 35 patents.^[4] He is known for characterizing the mechanisms by which skeletal muscle undergoes atrophy and hypertrophy.

Glass is also a playwright. His play, "Love + Science" was produced Off-Broadway in New York City in 2023.^[5]

Scientific career

Glass helped to identify the mechanism by which muscles connect to nerves. Glass and his colleagues, including George Yancopoulos, discovered a receptor tyrosine kinase which they named "MuSK" (Muscle Specific Kinase, or MuSK protein). They went on to show that MuSK is required for the formation of the neuromuscular junction, the key structure which allows motor neurons to induce skeletal muscle to contract.^[6] They next demonstrated that the ligand for MuSK is agrin, a protein secreted by the motor neuron to induce formation of the neuromuscular junction.^[7]

Glass also cloned receptors for neurotrophic factors, such as TrkB, the receptor for BDNF, and showed that they were sufficient to mediate signaling without the requirement of the Low affinity Nerve Growth Factor receptor (LNGFR).^[8]

Glass identified the E3 ubiquitin ligases, MuRF1 and FBXO32/Atrogin1/MAFbx, which are upregulated during skeletal muscle atrophy; mice which are null for these ligases were found to have less loss of muscle under atrophic conditions.^[9]. One substrate of MuRF1 is Myosin heavy chain (MHC), a major component of the sarcomere^[10]. Therefore, by degrading MHC, MuRF1 breaks down a major component of skeletal muscle, inducing muscle to atrophy.

Glass further identified the Akt pathway as being critical for inducing skeletal muscle to undergo hypertrophy.^[11]. Briefly, the growth factor IGF1 induces muscle to hypertrophy, or expand in size, via the increase in size of the pre-existing muscle fibers. This happens by IGF1/IGF1R/PI3K/Akt signaling, which in turn both activates the mTOR pathway to increase protein synthesis, and inhibits the activation of MuRF1, by blocking nuclear translocation of the Foxo family of transcription factors ^[12].

He was elected to both the National Academy of Sciences^[13] and the American Association for the Advancement of Science. Earlier, he was elected to the American Society for Clinical Investigation.^[14]

Book on Experimental Design, and a Critique of Hypothesis-testing

David Glass is the author of a book aimed at teaching students how to design biology experiments, titled "Experimental Design for Biologists." The book is in its 2nd edition, published by Cold Spring Harbor Laboratory Press.^[15] In the initial chapters of his book, Glass argues against hypothesis testing as a framework for performing experiments, and instead suggests that experiments should initially be framed with questions, in order to stimulate the production of data. Once there is data, then that can be used to produce a model, which can next be tested for its predictive power. While he doesn't mention Bayesian reasoning, these suggestions are reminiscent of Bayesian methods. Glass also argued against hypothesis testing in an article titled, "A critique of the hypothesis, and a defense of the question, as a framework for experimentation.".^[16]

Skeletal Muscle Journal

Glass was the founding editor-in-chief of the Elsevier journal Skeletal Muscle.^[17]

Theater

Glass wrote "Love + Science", which was produced Off-Broadway at City Center in New York City in the summer of 2023, and was reviewed by the New York Times,^[18] and by the editor-in-chief of Science, in Science (journal).^[19]

Key Papers

• Glass DJ, Nye SH, Hantzopoulos P, et al. (July 1991). "TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor". Cell. 66 (2): 405–13. doi:10.1016/0092-8674(91)90629-D. PMID 1649703. S2CID 43626580.
• DeChiara TM, Bowen DC, Valenzuela DM, et al. (May 1996). "The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo". Cell. 85 (4): 501–12. doi:10.1016/S0092-8674(00)81251-9. PMID 8653786. S2CID 17455481.
• Glass DJ, Bowen DC, Stitt TN, et al. (May 1996). "Agrin acts via a MuSK receptor complex". Cell. 85 (4): 513–23. doi:10.1016/S0092-8674(00)81252-0. PMID 8653787. S2CID 14930468.
• Bodine S, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD (2001). "Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo". Nat Cell Biology. 3 (1): 1014–1019. doi:10.1038/ncb1101-1014. PMID 11715023.
• Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ (2001). "Identification of ubiquitin ligases required for skeletal muscle atrophy". Science. 294 (5547): 1704–1708. Bibcode:2001Sci...294.1704B. doi:10.1126/science.1065874. PMID 11679633.

Honors & Awards

Honors – elected member

• American Society for Clinical Investigation (2004)
• American Association for the Advancement of Science (2023)
• National Academy of Sciences (2024)