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Alana M. O'Reilly, PhD

Alana M. O'Reilly, PhD

Associate Professor

Director, Immersion Science Program

Research Program

 

Educational Background

  • PhD, Cell and Developmental Biology, Harvard University, Cambridge, MA
  • BA, Chemistry, University of Pennsylvania, Philadelphia, PA

 

Honors & Awards

  • Early Research Investigator Award, Temple University School of Medicine, 2012

Research Program

Research Interests

Nutritional mechanisms that influence stem cell function and development

  • Molecular mechanisms of Hedgehog signaling regulation by dietary cholesterol during development and in cancer
  • Role of Hedgehog signaling in controlling epithelial stem cell lifetime
  • Influence of dietary supplements on developmental events
  • Development of a crowdsourcing model for cancer research in partnership with Philadelphia area high school students and teachers

Lab Overview

Decades of research have demonstrated that a balanced diet is elemental for human health. Malnutrition affects all socioeconomic levels and cultures, with particular impact on individuals in low resource settings. However, our understanding of how individual nutrients effect the cellular changes associated with aberrant states is at its infancy. The underlying hypothesis for our work is that each component of a balanced diet influences signal transduction pathways in target cells, resulting in a collective developmental response within tissues. Our goal is to map the signal transduction pathways targeted by individual nutrients in vivo, in order to build a comprehensive mechanistic understanding of how dietary imbalance affects normal development and identify inexpensive, widely accessible interventions to reduce and treat cancer and other diseases.

Dietary cholesterol controls stem cell proliferation via Hedgehog (Hh) signaling

Our lab recently identified a novel mechanism that translates levels of dietary cholesterol to control proliferation of a single cell population, epithelial Follicle Stem Cells (FSCs), within the Drosophila ovary. Cholesterol levels are sensed by its protein receptor (DHR96) within a subpopulation of ovarian cells that produce the growth factor Hedgehog (Figure 1). In starved flies, Hh is held on the producing cells by the transmembrane protein Boi. Upon feeding, cholesterol binds to its receptor and triggers the activation of a series of proteins to alter the structure of Boi, promoting Hh release and driving stem cell proliferation. Thus, cholesterol consumption regulates the balance between Boi-mediated Hh sequestration and release, allowing for a rapid response to changes in nutrient status and providing a mechanism for controlling egg production rates based on availability of nutrients that assure progeny survival. Current efforts are focused on defining the biochemical changes that mediate Hh release, determining the downstream consequences of Hh release within FSCs, and assessing the contribution of this mechanism to cancer.

Stem Cell Communication within the niche

One striking finding from our work is that FSCs exhibit long, axon-like projections that may mediate communication between stem cells and other cells within the niche. A genetic screen performed in the lab uncovered a number of genes that appear to control FSC projection dynamics and interactions with other cell types.  Current work focuses on determining the biological effects of altering gene function on stem cell lifetime and communication between cells within the niche.

Mapping nutrient targets during development

An unusual aspect of our lab is a large number of high school student trainees who participate directly in our research.  The research branch of our Immersion Science program for high school students (Link to new page focused on Immersion Science research here (see attached form) aims to determine the direct molecular targets of dietary nutrients by determing their developmental effects in varied genetic backgrounds in the fly. This work involves hundreds of high school students in the FCCC Teaching Lab here on campus and in high school classrooms in Philadelphia and the surrounding counties, as well as graduate students and postdoctoral fellows who follow-up initial results from the program with advanced approaches.  We have found that high school students produce reproducible, high quality data that is in peer-reviewed publications, suggesting that crowdsourcing of cancer-relevant experiments among hundreds of students is a successful and inexpensive approach to large-scale understanding of the roles of specific nutrients in development. Current work focuses on nutrients that target the Ras, Hedgehog, and nuclear hormone receptor signaling pathways. 

People

Tanu Singh MS

Graduate Student Drexel University College of Medicine

Room: R354
215-214-3219

Amanda Browne

Undergraduate Researcher, Boston University

Room: R354
215-214-3219

Benjamin Neubert

North Penn HIgh School

Dara M. Ruiz-Whalen, MSEd

Immersion Science Program Coordinator

Room: R345
215-728-2858

Brian Mileknki

Immersion Science Program

Room: W451
215-728-5320

Caroline Pritchard

Immersion Science Program

Room: R340
215-728-2858

Angela Le

Immersion Science Program

Room: R340
215-728-2858

Shannon Robins

Immersion Science Program

Room: W345
215-214-1650

Jessica Vadaketh

Immersion Science Program

Room: W364
215-728-3563

Allison Biester

Immersion Science Program

Room: R422
215-728-3669

Victoria McGovern

Immersion Science Program

Room: P3165
215-728-3669

Cassie Stapf

Immersion Science Program

Room: P3019
215-728-4013

Tess Konnovitch

Immersion Science Program

Room: R354
215-214-3219

Priya Zaveri

Immersion Science Program

Room: W363
215-728-3648

Additional Staff

Ernest Boamah, PhD, Immersion Science instructor 2013

Todd Strochlic, VMD, PhD, Immersion Science instructor 2013

Ryan Henry, PhD, Immersion Science instructor, 2014

Maria Radu, PhD, Immersion Science instructor, 2014,

Christopher Aichele, MSEd, Immersion Science instructor, 2015

Former Staff Members

Erin Ventresca (Assistant Professor, Albright College)

Daniel Zinshteyn (PhD candidate, Cornell University)

Heather Schofield (MD/PhD candidate, University of Michigan)

Kevein Stavrides (MD candidate, Drexel University College of Medicine)

Anthony Judice (DO candidate, Pennsylvania College of Osteopathic Medicine)

Anthony Hopkins, (BSE candidate University of Pittsburgh)

 

The Immersion Science Program

The Immersion Science program aims to train high school students in cutting edge biomedical research. Students participate in courses in the FCCC Teaching laboratory in the Reimann Building or in their home classrooms, conducting novel research to define the cancer signals targeted by nutrients.  The program has dual goals: 1) to develop the pipeline of diverse cancer researchers by educating of hundreds of high school students each year in the conceptual and experimental approaches used in FCCC laboratories, and 2) to provide new understanding of the effects of dietary changes on normal and cancer cells, and to better understand how components of a patient's diet might affect the treatment of his/her cancer.  Immersion Science students follow-up their initial discoveries from the course in a dozen (and growing) FCCC research labs, creating a collaborative, multi-faceted, and comprehensive research network to address this problem.  

Former Staff, Immersion Science

Devon Riggs, Adam Bolotsky, Cal McAuliffe, Danielle Talbot, Benjamin Strekha, Sanat Deshpande, Ethan Silver, Yvegniya Miglo, Manali Shah, Raj Madhani, Vignesh Murali, Laura Leonard, Hannah Mumber

External Affiliations

Adjunct Associate Professor, Drexel University College of Medicine Department of Biochemistry

Adjunct Associate Professor, Temple University Medical School Department of Biochemistry

Selected Publications

Hartman, T.R., Ventresca, E.*, Hopkins, A.*, Zinshteyn, D.E., Singh, T., O’Brien, J.A., Neubert, B.C., Hartman, M.G., Schofield, H.K., Stavrides, K.P., Talbot, D. E., Riggs, D. J., Pritchard, C., O’Reilly, A.M.  Novel tools for genetic manipulation of Follicle Stem Cells in the Drosophila ovary reveal an integrin-dependent transition from quiescence to proliferation. Genetics, 114.173617 PubMed  

Hartman, T.R., Strochlic, T.I., Ji, Y., Zinshteyn, D., O’Reilly, A.M. Diet controls Drosophila follicle stem cell proliferation via Hedgehog sequestration and release. J. Cell Biol. 201:741-757, 2013 PubMed

Additional Publications

My NCBI