Ryan M. Young, Ph.D.

Ryan M. Young, Ph.D.
Investigator
NIH Stadtman Investigator

Dr. Young employs proteogenomic technologies to elucidate novel modes of pathogenic signaling in multiple myeloma and lymphoma. Insights from his research are helping to identify novel therapeutic targets and to exploit druggable pathways in lymphoid malignancies.

Areas of Expertise

1) multiple myeloma, 2) lymphoma, 3) functional genomics, 4) B cell biology, 5) signal transduction, 6) proteomics

Contact Info

Ryan M. Young, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 10, Room 4N108
Bethesda, MD 20892
Ph: 240-858-3513
youngrm@nih.gov

Multiple myeloma (MM) is an incurable malignancy of plasma cells marked by extreme genetic and phenotypic heterogeneity. Chromosomal hyperdiploidy or recurrent chromosomal translocations involving the immunoglobulin heavy chain locus primarily characterize this disease, with an abundance of mutations chiefly targeting the RAS and NF-kB pathways. While the genetics of MM have been well-annotated, much less is known about pathogenic signaling in MM and how common mutations contribute to oncogenic signaling. My research program utilizes cutting-edge proteogenomic techniques, high-resolution microscopy imaging and biochemical approaches to elucidate molecular mechanisms underlying oncogenic signaling in MM. The goal of my lab is to find new opportunities for the targeted treatment of MM by exploiting druggable pathways, even in tumors with undruggable driver oncogenes.

Current projects in the laboratory focus on: 1) discovering new modes of pathogenic signaling emanating from mutant KRAS and NRAS in MM;  2) characterizing the origins of NF-kB survival signaling that is prevalent in MM; and 3) identifying novel genes that control protein stability of commonly expressed oncogenes and tumor suppressors in lymphoid malignancies.

NIH Scientific Focus Areas:
Cancer Biology, Cell Biology, Genetics and Genomics, Molecular Biology and Biochemistry, Molecular Pharmacology
  1. Phelan JD, Young RM, Webster DE, Roulland S, Wright GW, Kasbekar M, Shaffer AL 3rd, Ceribelli M, Wang JQ, Schmitz R, Nakagawa M, Bachy E, Huang DW, Ji Y, Chen L, Yang Y, Zhao H, Yu X, Xu W, Palisoc MM, Valadez RR, Davies-Hill T, Wilson WH, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Rodriguez FJ, Estephan F, Holdhoff M, Kruhlak MJ, Hewitt SM, Thomas CJ, Pittaluga S, Oellerich T, Staudt LM.
    Nature. 560(7718): 87-391, 2018. [ Journal Article ]
  2. Young RM, Wu T, Schmitz R, Dawood M, Xiao W, Phelan JD, Xu W, Menard L, Meffre E, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Staudt LM.
    Proceedings of the National Academy of Science U S A. 112(44): 13447-54, 2015. [ Journal Article ]
  3. Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM.
    Nature. 470(7332): 115-9, 2011. [ Journal Article ]
  4. Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM.
    Nature Medicine. 21(8): 922-6, 2015. [ Journal Article ]
  5. Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, Wright G, Shaffer AL, Hodson DJ, Buras E, Liu X, Powell J, Yang Y, Xu W, Zhao H, Kohlhammer H, Rosenwald A, Kluin P, Müller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Ogwang MD, Reynolds SJ, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pittaluga S, Wilson W, Waldmann TA, Rowe M, Mbulaiteye SM, Rickinson AB, Staudt LM.
    Nature. 490(7418): 116-20, 2012. [ Journal Article ]

Dr. Young received his B.S. from Worcester Polytechnic Institute and his Ph.D. in Biochemistry from Cornell University in the laboratory of Drs. Barbara Baird and David Holowka.  His dissertation research described how lipid order in the plasma membrane controls signal transduction by regulating the activity of Src-family kinases.  He pursued post-doctoral training at National Jewish Medical Research Center in Denver, where he performed the first pre-clinical studies on inhibitors of B cell receptor signaling in lymphoma.  He next joined the laboratory of Dr. Louis Staudt at the National Cancer Institute and was later promoted to a staff scientist.  During this time Dr. Young developed a deep mechanistic understanding of how aggressive lymphomas utilize the B cell receptor and mutant isoforms of MYD88 to promote tumor growth and survival.  These insights have helped to refine the use of B cell receptor pathway inhibitors in the clinic.  His current research aims to elucidate pathological signaling in lymphoid malignancies, including multiple myeloma and lymphoma, and leverage these discoveries to develop novel diagnostic and therapeutic strategies.