Joanna Phillips, MD, PhD

Assistant Professor
Department of Neurological Surgery
+1 415 514-4929
Research Overview: 

In our laboratory we are interested in determining how interactions in the brain tumor microenvironment help drive tumorigenesis and invasion. Glioblastoma (GBM), a highly malignant brain tumor of adults and children, is characterized by diffuse invasion and abnormal activation of receptor tyrosine kinase signaling pathways. Despite many advances in our understanding of the biology of these tumors their treatment remains challenging. In the laboratory, we use both in vivoand ex vivo model systems to study the interaction between tumor cells and the microenvironment including microglia, macrophages, reactive astrocytes, and the extracellular matrix. These studies are designed to identify novel determinants of gliomagenesis with potential for therapeutic targeting. In addition, we are investigating proteoglycans and their glycosaminoglycan (GAG) side chains as potential diagnostic and prognostic brain tumor biomarkers.

Proteoglycans regulate oncogenic signaling in brain tumors.  In the brain, extracellular proteoglycans play critical roles in the regulation of cell signaling, migration, and differentiation via their interactions with extracellular ligands, growth factor receptors, extracellular matrix components, and intracellular proteins. In addition, proteoglycans help regulate the inflammatory response. Heparan sulfate and chondroitin sulfate proteoglycans (HSPGs and CSPGs) are abundant in GBM, and in the laboratory we are studying the cellular and molecular mechanisms by which alterations in proteoglycan core protein expression, GAG synthesis, and sulfation help drive brain tumorigenesis. As a part of these studies, we are also testing ways to therapeutically target proteoglycans and to use them as blood biomarkers of disease.

Role of the innate immune response in brain tumor development and invasion.  The innate immune response, particularly the macrophage response, is known to play an important role in disease for many peripheral cancers.  While microglia/macrophages are abundant in human glial tumors their function in disease is largely unknown. Using human tumor samples, we have demonstrated that GBM subtypes differ with respect to both the number of microglia/macrophages and the expression of immune response genes, including microglia/macrophage signature genes. To identify the function of glioma-infiltrating microglia/macrophages we are taking three approaches: 1) Compare the inflammatory infiltrate in human brain tumors from different anatomical sites and from different tumor types, including infiltrative and non-infiltrative tumors, by flow cytometry and expression profiling in; 2) determine the function of microglia/macrophages in murine malignant astrocytomas using genetic and chemical methods to alter their behavior; and 3) directly visualize how microglia/macrophages influence tumor cell behaviors in vivo and ex vivoin brain tumor slice cultures.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Neurobiology
Research Summary: 
Tumor-microenvironment interactions regulating brain tumorigenesis

Websites

Publications: 

CXCL14 promotes a robust brain tumor-associated immune response in glioma.

Clinical cancer research : an official journal of the American Association for Cancer Research

Kumar A, Mohamed E, Tong S, Chen K, Mukherjee J, Lim Y, Wong CM, Boosalis Z, Shai A, Pieper RO, Gupta N, Perry A, Bollen AW, Molinaro AM, Solomon DA, Shieh JTC, Phillips JJ

Targeted Next-Generation Sequencing Reveals Divergent Clonal Evolution in Components of Composite Pleomorphic Xanthoastrocytoma-Ganglioglioma.

Journal of neuropathology and experimental neurology

Lucas CG, Davidson CJ, Alashari M, Putnam AR, Whipple NS, Bruggers CS, Mendez JS, Cheshier SH, Walker JB, Ramani B, Cadwell CR, Sullivan DV, Lu R, Mirchia K, Van Ziffle J, Devine P, Goldschmidt E, Hervey-Jumper SL, Gupta N, Oberheim Bush NA, Raleigh DR, Bollen A, Tihan T, Pekmezci M, Solomon DA, Phillips JJ, Perry A

Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas.

Journal of neuro-oncology

Autry AW, Lafontaine M, Jalbert L, Phillips E, Phillips JJ, Villanueva-Meyer J, Berger MS, Chang SM, Li Y

Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities.

Nature genetics

Choudhury A, Magill ST, Eaton CD, Prager BC, Chen WC, Cady MA, Seo K, Lucas CG, Casey-Clyde TJ, Vasudevan HN, Liu SJ, Villanueva-Meyer JE, Lam TC, Pu JK, Li LF, Leung GK, Swaney DL, Zhang MY, Chan JW, Qiu Z, Martin MV, Susko MS, Braunstein SE, Bush NAO, Schulte JD, Butowski N, Sneed PK, Berger MS, Krogan NJ, Perry A, Phillips JJ, Solomon DA, Costello JF, McDermott MW, Rich JN, Raleigh DR

Prospective genomically-guided identification of 'early/evolving' and 'undersampled' IDH-wildtype glioblastoma leads to improved clinical outcomes.

Neuro-oncology

Zhang Y, Lucas CG, Young JS, Morshed RA, McCoy L, Oberheim Bush NA, Taylor JW, Daras M, Butowski NA, Villanueva-Meyer JE, Cha S, Wrensch M, Wiencke JK, Lee JC, Pekmezci M, Phillips JJ, Perry A, Bollen AW, Aghi MK, Theodosopoulos P, Chang EF, Hervey-Jumper SL, Berger MS, Clarke JL, Chang SM, Molinaro AM, Solomon DA