Duncan Dam, PhD
Dr. Dam received his PhD in Chemistry from Northwestern University, working in Dr. Teri Odom’s laboratory on the use of aptamer-loaded gold nanoconstructs for targeted cancer therapeutics. Dr. Dam also verified the physical interactions of the nanoconstructs with its targeted protein, which helped to explain the mechanism of cancer cell death. In July, 2014, Dr. Dam joined the Paller laboratory and the Training Grant to advance his nanotechnology and chemistry background towards translational biology.
Using sophisticated instrumentation in our Center for Advanced Microscopy, Dr. Dam studied the membrane-based molecular mechanism for activation of IGF-1 receptor in normal keratinocytes, including with GM3 depletion. He studied how GM3-mediated "insulin resistance" in diabetes suppresses keratinocyte insulin/IGF-1 receptor signaling, especially given the major role of GM3 as a lipid raft organizer. He discovered an alternate, flotillin-dependent, clathrin-mediated endocytosis pathway for IGF-1 receptor internalization and signaling in normal human epidermal keratinocytes (NHEKs). These data suggest that IGF1R endocytosis and signaling are controlled by clathrin-dependent endocytosis, mediated by one of two adaptors: flotillin in noncaveolar lipid rafts or the αAP1/2 complex in clathrin pits. His discovery of a flotillin-dependent, clathrin-mediated endocytosis pathway for IGF1R provides a new avenue for drug discovery for diseases with aberrant regulation of IGF1R signaling. He has also been investigating how spherical nucleic acid nanoconstructs are internalized into cells and 3D skin models, and has similarly discovered a role for flotillin in basal keratinocyte nanoparticle uptake using specific epidermal scavenger receptors. Dr. Dam also explored how spherical nucleic acids (SNAs), which are gene regulating nanoconstructs, are taken up so ready into cells and through epidermis. Building on work that showed the key role of scavenger receptors in skin, he discovered a flotillin-scavenger receptor 3 complex in noncaveolar raft domains that is critical for cell uptake. Dr. Dam has assumed "ownership" of the epidermal scavenger receptor field towards his independent direction.
Dr. Dam also worked with diet-induced obese and genetic diabetic mouse wound healing models. The laboratory has previously shown the efficacy of topically-delivered GM3 synthase siRNA spherical nucleic acids (SNAs) in reversing the poor wound healing in diet-induced obese diabetic mice. He has been part of a team comparing these SNAs with small molecule inhibitors that reduce GM3 content for the wound healing defect in diabetic mice.
Dr. Dam has given oral presentations at the 2016 and 2017 Society of Investigative Dermatology meetings as well as 2016 Material Research Society meeting. Dr. Dam and Dr. Paller are part of a consortium between NU and Nanyang Technology Institute (Singapore), evaluating a topically applied photoactivatable nanoconstruct for squamous cell carcinoma; Dr. Dam has given oral presentations on these nanoconstructs at the NTU-NU Nanomedicine Institute Workshop in 2016 (Maui, HI) and 2017 (Santa Barbara, CA).
His Mentoring Team consisted of Drs. Paller, Lavker, Bass (Chief of Endocrinology and an expert in insulin signaling), and Quaggin (Chief of Nephrology/head of the Bluhm Cardiovascular Institute, who has found GM3 to bind to soluble FLT1 in podocytes and regulate pericyte behavior). Dr. Dam has published a 1st author paper, a book chapter (on wound healing), has submitted 1 first-author paper and 1 book chapter. He is currently writing 2 additional papers. He continued his postdoctoral training for an additional year beyond the T32 years, and is applying for academic positions, ideally continuing his cutaneous biology studies.
Dr. Dam has received grant awards from the CBC (for Proteomics research) and from the Developmental Therapeutic Center (to utilize a new NanoBRET technique).
Publications
Dam DHM, Wang XQ, Lee S, Shipp D, Vijay M, Joo Y, Paller AS. Ganglioside GM3 mediates glucose-induced suppression of IGF-1 receptor-Rac1 activation to inhibit keratinocyte motility. J Invest Dermatol, 137: 440-448, 2017. PMID: 27729281.
Dam DHM, Jelsma SA, and Paller AS. Invited Book Chapter in “Wound healing in Diabetes”, “Impaired wound healing in diabetic ulcers: accelerated healing through depletion of ganglioside,” 2017, in press.
Song QQ*, Dam DHM*, Briley W, Roth EW, Wang X-Q, Mirkin CA, and Paller AS. Class A scavenger receptors promote skin penetration of spherical nucleic acids by a flotillin-1 dependent process. ACS Nanom 2017, submitted (*, authors contributed equally).
Dam DHM, Paller AS. In “Gangliosides in Health and Disease”, Gangliosides in wound healing and pain. (Eds., Schnaar RL, Lopez, PHH). Elsevier. Submitted, 2017.
Abstracts
Dam DHM, Jelsma S, and Paller AS. Discovery of an alternate, flotillin-dependent, clathrin-mediated endocytosis pathway for IGF-1 receptor internalization and signaling in keratinocytes. J Invest Dermatol, 136:S79, 2016.
Dam DHM, Jelsma S, and Paller AS. Ganglioside GM3, which mediates insulin resistance, disrupts insulin/IGF 1 receptor heterodimer. J Invest Dermatol, 137: S93, 2017.
Dam DHM, Zhao L, Jelsma S, Zhao Y, and Paller AS. Ultra-small nanoparticle-based platform for photodynamic skin cancer therapy. J Invest Dermatol, 137:S118, 2017.