Dr. Megan Dennis
Associate 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 2019, a R15 grant was awarded to advance undergraduate research at Marist.
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.
Recently, my research has expanded to include the identification and study of novel bacteriophage through the SEA-PHAGES program, in collaboration with the University of Pittsburgh & the Howard Hughes Medical Institute. Bacteriophage are tiny viruses which infect different types of bacterial hosts and have been used in medical and agricultural settings to control bacterial infections including infection by bacteria which have developed antibiotic resistance. Since most types of bacteriophage only infect a small group of bacterial hosts, this type of phage therapy/treatment can eliminate harmful bacteria while leaving beneficial microbial communities intact. Working with first-year students at Marist, we have isolated new types of phage from sites around campus and characterized their morphological and genetic traits. In the future, students will continue to characterize their phage, including studies to understand the types of bacterial hosts which each phage can infect and kill.
Bowman SL, Le L, Zhu Y, Sitaram A, Tenza D, Sviderskaya EV, Bennett DC, Bonifacino JS, Raposo G, Owen DJ, Dennis MK, and Marks MS. (2021) A BLOC-1: AP-3 super-complex sorts a cis-SNARE complex into recycling endosomal tubular transport carriers. Journal of Cell Biology, 220(7): e202005173. doi: 10.1083/jcb.202005173. Epub 2021 April 22.
Le L, Escobar IE, Ho T, Lefkovith AJ, Latteri E, Dennis MK, Haltaufderhyde KD, Sviderskaya EV, Bennett DC, Oancea E, and Marks MS. (2020) SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation. Mol Biol Cell, 32(24): 2687-2702; doi: 10.1091/mbc.E20-03-0200
Ripoll L, Heiligenstein X, Hurbain I, Domingues L, Figon F, Petersen KJ, Dennis MK, Houdusse A, Marks MS, Raposo G, and Delevoye C. (2018) Myosin VI and branched actin filaments mediate membrane constriction and fission of melanosomal tubule carriers. Journal of Cell Biology, 217(8): 2709-2726. doi: 10.1083/jcb.201709055. Epub 2018 Jun 6.
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
2021-2024 National Institutes of Health Academic Research Enhancement Award (R15): Chromatin-mediated maintenance of genomic integrity in germ cells. NICHD 1R15HD103115; $346,418.
2019-2023 National Institutes of Health Academic Research Enhancement Award (R15): Role of AP-3 in protein sorting and autophagy in melanosome biogenesis. NIGMS 1R15GM132810; $379,914.
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.