Our research focuses on cell cycle control in cerebellar development and medulloblastoma, a pediatric brain tumor that arises in the cerebellum. These tumors are the most common solid malignancy of childhood. Current treatments for medulloblastomas include surgical resection, chemotherapy, and cranio-spinal irradiation. These therapies lead to an ~60% "cure" rate, but survivors are left with life long devastating side effects as a result of these treatments. It is our hope that by gaining increased insight into the cellular and molecular mechanisms that drive tumor establishment, growth, and recurrence (which is fatal) we can identify genes and proteins whose activity could in the future be modulated by drugs and novel small molecules, thereby ameliorating the need for irradiation and chemotherapy and improving quality of life for survivors.

Medulloblastomas can be divided into four molecularly and histologically distinct subclasses, one of which is typified by activation of a pathway called Sonic hedgehog (SHH). This subclass is proposed to arise from rapidly proliferating cerebellar neural precursors, which depend on Shh for their cell division during development. We study how Shh drives proliferation through its interactions with other developmentally regulated pathways, such as the Hippo pathway, insulin-like growth factor (IGF) pathway, and the mTOR pathway, which drives new protein synthesis in response to growth factor signaling.

The workhorse of the lab is primary cerebellar culture derived from the neonatal mouse cerebella. These cells can be maintained in culture in serum free medium; the addition of purified Shh to the medium maintains them in a proliferative state for approximately 72 hours. We can manipulate the cells pharmacologically or genetically (using retroviruses and shRNA-carrying lentiviruses) and observe effects on proliferation and pathway activation using common cell biological techniques. These studies are complemented with histological analysis of the developing cerebellum. We also use mice that have been genetically modified so that the Shh pathway is constitutively activated in the developing cerebellum.  These mice develop medulloblastomas that closely resemble those of the human subclass of medulloblastoma associated with activated Shh signaling. We analyze these tumors and manipulate them in organotypic slice cultures as well as dissociated primary cultures. Current projects in the lab we are studying include medulloblastoma radiation resistance, metabolism, and tumor immune microenvironment. 

Leon McSwain, BS 

Education: Graduate student, Emory University Cancer Biology PhD Program

Current Project: Studying how phosphorylation of the small DNA/RNA/protein binding factor YB1 regulates is role in DNA damage repair and RNA interactions.  YB1 is a downstream effector of Yes-associated protein and is up-regulated in medulloblastoma

Fun Fact: President of the Emory Spokes Council (cycling advocacy group)

Email: leon.foy.mcswain@emory.edu


Victor Chen 

Education: Undergraduate student, Emory University 

Current Project: Preparing wild-type and phospho-mutant YB1 retroviruses

Email: victor.zilong.chen@emory.edu


Tiffany Huang 

Education: Undergraduate student, Emory University 

Current Project: Studying how NADPH Oxidase 4 (NOX4) contributes to medulloblastoma growth and radiation resistance

Email: tiffany.huang@emory.edu


Anu Dhanashekar 

Education: Undergraduate student, Emory University 

Current Project: Learning cell biology laboratory skills and assisting with a number of projects

Email: anu.dhanashekar@emory.edu

Bobby Bhatia, PhD

Dane Campbell, MD

Abhinav Dey, PhD

James Felker, MD

Africa Fernandez-Lopez, PhD

Anshu Malhotra, PhD

Victor Maximov, PhD

Susana Parathath, PhD

Chad Potts, BS

Lori Mainwaring Ramkissoon, PhD

Hope Robinson, PhD

Caroline Roe, BS

Rachel Rotenberry, BS

Nithya Shanmugam (pre-med student)

Yun Wei, PhD

Robinson MH, Maximov V, Lallani S, Farooq H, Taylor MD, Read RD, Kenney AM.  Upregulation of the chromatin remodeler HELLS is mediated by YAP1 in Somic hedgehog medulloblastoma.  (2019) Scientific Reports Sept 20; 9(1).

Maximov V, Chen Z, Wei Y, Robinson MH, Herting CVJ, Shanmugam NS, Rudneva V, Goldsmith KC, MacDonald TJ, Northcott PA, Hambardzumyan D, Kenney AM.  Tumor-associated macrophages exhibit anti-tumoral properties in Sonic hedgehog medulloblastoma.  (2019) Nature Communications June 3; 10(1):2014

Eyrich N, Potts C, Robinson MH, Kenney AM.  HIF1a is stabilized in Sonic hedgehog stimulated proliferating cerebellar progenitor cells in an NADPH oxidase-dependent manner. (2019) April, Volume 39 (8) Molecular and Cellular Biology

Wei Y, Maximov V, Morrissy SA, Taylor MD, Pallas DC, Kenney AM.  Inhibitor 2 of phosphatase 2A compromises p53 function in Sonic hedgehog medulloblastoma (2019) Molecular Cancer Research 17:186-198.


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National Institutes of Health: R01 - Y-box1 and normoxic HIF1a in Sonic hedgehog medulloblastoma tumor stem cell radiation resistance  

Alex’s Lemonade Stand Foundation: Innovation Award  - The anti-tumor immune microenvironment in the Sonic hedgehog subclass of medulloblastoma