School of Science
Science and Allied Health 217
(845) 575-3000 ext. 2734
Dr. Megan Dennis
Assistant Professor of Biology
Postdoctoral Fellow, Pathology & Laboratory Medicine, University of Pennsylvania School of Medicine & Children’s Hospital of Philadelphia. Philadelphia, PA. 2010-2016.
Visiting Instructor, Biology, Rutgers University-Camden. Camden, NJ. 2011-2012.
PhD, Biomedical Sciences, University of New Mexico School of Medicine
BS, Biology, Philosophy (minor), Gonzaga University
Research Interests / Areas of Focus
My research interests center around the biogenesis of lysosome related organelles (LROs). LROs are found in a diverse array of cell types in the human body, including melanocytes (the pigment-producing cells of the hair, skin and eyes), lung epithelial cells, platelets and immune cells. In each of these cell types, LROs coexist with classical lysosomes, indicating that cells producing LROs have additional trafficking machinery to route cargoes towards LROs and away from classical lysosomes; however, this trafficking machinery is incompletely understood. Additionally, defects in LRO biogenesis result in a number of diseases, including Hermansky-Pusdlak, Griscelli and Chediak-Higashi syndromes.
In the lab, we use immortalized mouse melanocytes as a model system for investigating LRO biogenesis. These cells are amenable to a range of cell biology techniques, ranging from microscopy to biochemistry, and we have cell lines from mouse models of Hermansky-Pudlak Syndrome to investigate roles for individual proteins in LRO biogenesis. Additionally, the cells undergo a significant phenotypic change when LRO biogenesis is impaired -- shifting from pigmented to hypopigmented -- which provides a rapid mechanism for phenotypic screening of new and novel mediators of LRO biogenesis.
Dennis MK, Delevoye C, Acosta-Ruiz A, Hurbain I, Romao M, Hesketh GG, Goff PS, Sviderskaya EV, Bennett DC, Luzio JP, Galli T, Owen DJ, Raposo G, and Marks MS. (2016) BLOC-1 and BLOC-3 regulate VAMP7 cycling to and from melanosomes via distinct tubular transport carriers. Journal of Cell Biology, 214(3): 293-308. doi: 10.1083/jcb.201605090.
Delevoye C, Heiligenstein X, Ripoll L, Gilles-Marsens F, Dennis MK, Linares RA, Derman L, Gokhale A, Morel E, Faundez V, Marks MS, and Raposo G. (2016) BLOC-1 brings together the actin and microtubule cytoskeletons to generate recycling endosomes. Current Biology. 26(1):1-13. doi: 10.1016/j.cub.2015.11.020. Epub 2015 Dec 24.
Dennis MK*, Mantegazza AR*, Snir OL, Tenza D, Acosta A, Delevoye C, Zorger R, Sitaram A, de Jesus-Rojas W, Ravichandran K, Rux J, Sviderskaya EV, Bennett DC, Raposo G, Marks MS, and Setty SRG. (2015) BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery. Journal of Cell Biology, 209(4): 563-577. doi: 10.1083/jcb.201410026. *Contributed equally
*Petrie WK, *Dennis MK, Hu C, Dai D, Arterburn JB, Smith HO, Hathaway HJ, Prossnitz ER. (2013) G protein-coupled estrogen receptor (GPER)-selective ligands modulate endometrial tumor growth. Obstetrics and Gynecology International, vol. 2013, Article ID 472720. doi:10.1155/2013/472720. *Contributed equally.
Burai R, Ramesh C, Nayak TK, Dennis MK, Bryant BK, Prossnitz ER, Arterburn JB. (2012) Synthesis and characterization of tricarbonyl-Re/Tc(I) chelate probes targeting the G protein-coupled estrogen receptor GPER/GPR30. PLoS One, 7(10):e46861. doi: 10.1371/journal.pone.0046861. Epub 2012 Oct 15.
Sitaram A, Dennis MK, Chaudhuri R, De Jesus-Rojas W, Tenza D, Setty SR, Wood CS, Sviderskaya EV, Bennett DC, Raposo G, Bonifacino JS, Marks MS. (2012) Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes. Mol. Biol. Cell, 23(16): 3178-92. Epub 2012 June 20.
Nayak TK, Dennis MK, Ramesh C, Burai R, Atcher RW, Sklar LA, Norenberg JP, Hathaway HJ, Arterburn JB and Prossnitz ER. (2010) Influence of charge on cell permeability and tumor imaging of GPR30-targeted (111)In-labeled nonsteroidal imaging agents. ACS Chem Biol., 16;5(7): 681-90. Epub 3 June 2010.
Ramesh C, Nayak TN, Burai R, Dennis MK, Hathaway HJ, Sklar LA, Prossnitz ER, Arterburn JB. (2010) Synthesis and characterization of iodinated tetrahydroquinolines targeting the G protein-coupled estrogen receptor GPR30. J Med Chem. 53(3): 1004-1014. Epub 30 December 2009.
Dennis MK, Burai R, Ramesh C, Petrie WK, Alcon SN, Nayak TK, Bologa CG, Leitao A, Brailoiu E, Deliu E, Dun NJ, Sklar LA, Hathaway HJ, Arterburn JB, Oprea TI, Prossnitz ER. (2009) In vivo effects of a GPR30 antagonist. Nature Chemical Biology. 5(6): 421-427.
Blasko E, Haskell CA, Leung S, Gualtieri G, Halks-Miller M, Mahmoudi M, Dennis MK, Prossnitz ER, Karpus WJ, Horuk R. (2009) Beneficial role of the GPR30 agonist G-1 in an animal model of multiple sclerosis. J. Neuroimmunology. 214(1-2): 67-77. Epub 5 August 2009.
Dennis MK, Bowles HJ, MacKenzie DA, Burchiel SW, Edwards BS, Sklar LA, Prossnitz ER, Thompson TA. (2008) A multifunctional androgen receptor screening (MARS) assay using the high throughput Hyper-Cyt® flow cytometry system. Cytometry A. 73(5): 390-399.
Awards and Honors
2012-2015 Ruth L. Kirschstein National Research Service Award (NRSA) Postdoctoral Fellowship. NIAMS 1F32AR062476.
2010-2012 Penn-Postdoctoral Opportunities in Research & Teaching (Penn-PORT) Postdoctoral Fellowship. NIH Institutional Research and Academic Career Development Award (IRACDA). NIGMS K12GM081259.