RESEARCH Albert Einstein College of Medicine Segall LAB PAGES


For most cancers, the cause of patient death is either local invasion into critical areas or metastasis - dissemination of tumor cells from the primary tumor to many parts of the body followed by formation of new tumors at those distant sites.  By understanding the mechanisms by which tumor cells invade and metastasize, we will have better chances of developing appropriate therapies.  Tumor cell motility and the orientation of tumor cells by chemotaxis make important contributions to invasion and metastasis.   

Three types of cancer are being studied.  Glioblastoma and head and neck cancer invade locally into critical areas and the primary tumors are not fully removable by surgery.  Breast cancer, although the primary tumor can be fully removed, metastasizes to distant sites, and the resulting metastases can lead to poor prognosis.  Tissue culture studies of invasion and signaling of these cancers are combined with in vivo analysis in mice.  Two types of in vivo approaches being used for studying invasion and metastasis: 1) injection of tumor cells into the orthotopic site (brain, floor of mouth, or mammary fat pad for glioma, head and neck cancer, and breast cancer respectively), and 2) formation of tumors in transgenic mice using oncogenes.  The injection assays allow the rapid molecular manipulation of cell lines to identify important signaling pathways that contribute to metastasis.  The transgenic mouse system provides a more clinically relevant model in which tumors develop from the appropriate tissue directly. 


The lab has also studied Dictyostelium discoideum and Saccharomyces cerevisiae. Dictyostelium and Saccharomyces provide a molecular/genetic dissection of chemotaxis. Both utilize G protein-coupled signal transduction pathways to mediate orientation responses. The movies sections demonstrate examples of these valuable model systems for studies of chemotaxis and directed cell responses.

Recent publications (NCBI PubMed Search for Segall, J.E.)

Donnelly SK, Cabrera R, Mao SPH, Christin JR, Wu B, Guo W, Bravo-Cordero JJ, Condeelis JS, Segall JE, Hodgson L. Rac3 regulates breast cancer invasion and metastasis by controlling adhesion and matrix degradation. J Cell Biol. 2017 216(12):4331-4349.

Huang YL, Segall JE, Wu M. Microfluidic modeling of the biophysical microenvironment in tumor cell invasion. Lab Chip. 2017 17(19):3221-3233. 

Jayakar SK, Loudig O, Brandwein-Gensler M, Kim RS, Ow TJ, Ustun B, Harris TM,  Prystowsky MB, Childs G, Segall JE, Belbin TJ. Apolipoprotein E Promotes Invasion in Oral Squamous Cell Carcinoma. Am J Pathol. 2017 187(10):2259-2272.

Jimenez L, Lim J, Burd B, Harris TM, Ow TJ, Kawachi N, Belbin TJ, Angeletti R, Prystowsky MB, Childs G, Segall JE. miR-375 Regulates Invasion-Related Proteins Vimentin and L-Plastin. Am J Pathol. 2017 187(7):1523-1536.

Coniglio S, Miller I, Symons M, Segall JE. Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion. J Vis Exp. 2016 Oct 20;(116).

Chiang SP, Cabrera RM, Segall JE. Tumor cell intravasation. Am J Physiol Cell  Physiol. 2016 311(1):C1-C14.

Jimenez L, Sharma VP, Condeelis J, Harris T, Ow TJ, Prystowsky MB, Childs G, Segall JE. MicroRNA-375 Suppresses Extracellular Matrix Degradation and Invadopodial Activity in Head and Neck Squamous Cell Carcinoma. Arch Pathol Lab Med. 2015 139(11):1349-61.

Jimenez L, Jayakar SK, Ow TJ, Segall JE. Mechanisms of Invasion in Head and Neck Cancer. Arch Pathol Lab Med. 2015 139(11):1334-48.

Zhou ZN, Sharma VP, Beaty BT, Roh-Johnson M, Peterson EA, Van Rooijen N, Kenny PA, Wiley HS, Condeelis JS, Segall JE. Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo. Oncogene. 2014 33(29):3784-93.

Coniglio SJ, Segall JE. Review: molecular mechanism of microglia stimulated glioblastoma invasion. Matrix Biol. 2013 32(7-8):372-80.

Ishihara D, Dovas A, Hernandez L, Pozzuto M, Wyckoff J, Segall JE, Condeelis  JS, Bresnick AR, Cox D. Wiskott-Aldrich syndrome protein regulates leukocyte-dependent breast cancer metastasis. Cell Rep. 2013 4(3):429-36. 

Entenberg D, Kedrin D, Wyckoff J, Sahai E, Condeelis J, Segall JE. Imaging tumor cell movement in vivo. Curr Protoc Cell Biol. 2013 Chapter 19:Unit19.7.

Friedl P, Locker J, Sahai E, Segall JE. Classifying collective cancer cell invasion. Nat Cell Biol. 2012 14(8):777-83.




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