Faculty / Research

Howard Crawford, PhD

Associate Professor  

 

Ph.D.: University of Texas Southwestern Medical Center at Dallas

Postdoctoral: Vanderbilt University

631-444-3085  howard.crawford@stonybrook.edu
Cancer/Mayo Clinic

Pancreatic cancer is the 5th most common cause of cancer related death in the United States. With about 30,000 Americans being diagnosed with pancreatic cancer each year, the disease incidence is relatively low compared to other cancers. However, with only a 4% 5-year survival rate, the prognosis for someone with pancreatic cancer is dismal. Successful treatment of pancreatic cancer is rare largely because it is difficult to detect at an early stage and, by the time it is detected, is largely resistant to standard chemotherapy.

 

My research is dedicated to dissecting the signal transduction pathways that lead directly to pancreatic tumor formation and progression in mouse models of pancreatic cancer.  By examining the chronic inflammation of the pancreas, which is a significant risk factor for later development of pancreatic cancer, we have identified shared pathways that control the formation of the aberrant epithelial structures in both inflamed and cancerous conditions, suggesting novel molecular targets for treatment of both conditions.

Song Y, Washington MK and Crawford HC.  Loss of FOXA1/2 is Essential for the Epithelial-to-Mesenchymal Transition in Pancreatic Cancer.  Cancer Research, In press

Bombardelli L, So E and Crawford HC.  Pancreas-specific ablation of b1 integrin induces tissue degeneration by disrupting polarized acinar cell secretion.  Gastroenterology, In press

Gibb DR, El Shikh M, Kang D-J, Rowe WJ, El Sayed R, Cichy J, Yagita H, Tew JG, Depsey PJ*, Crawford HC* and Conrad DH*.  ADAM10 is essential for Notch2-dependent Marginal Zone B cell development and CD23 cleavage in vivo.  J. Exp. Med, In press.  * Contributed equally to this manuscript.

Crawford HC, Dempsey PJ, Brown G, Adam L, ML Moss.  2009.  ADAM10 as a therapeutic target for cancer and inflammation.  Current Pharmaceutical Design.  15:  2288-2299. 

Guerriero JL, Ditsworth D, Fan Y, Zhao F, Crawford HC, and Zong W-X.  (2008). Chemotherapy induces tumor clearance independent of apoptosis.  Cancer Res, 68, 9595-960.

Rowehl RA, Crawford H,  Dufour A, Ju J and Botchkina GI.  Genomic Analysis of Prostate Cancer Stem Cells Isolated from a Highly Metastatic Cell Line.  (2008).  Cancer Genom. nd Proteom. 5, 301-310.

Botchkina IL, Rowehl RA, Rivadeneira DE, Karpeh MS Jr, Crawford H, Dufour A, Ju J, Wang Y, Leyfman Y, Botchkina GI.  (2009).  Phenotypic subpopulations of metastatic colon cancer stem cells: genomic analysis.  Cancer Genomics Proteomics. 2009 6:19-29.

Ardito CA, Briggs CD, Crawford HC.  (2008).  Targeting extracellular proteases in pancreatic cancer.  Exp. Opin. Therap. Targets. 12:  606-619.

McCawley LJ, Wright J, LaFleur BJ, Crawford HC and Matrisian LM.  Keratinocyte expression of MMP3 enhances differentiation and prevents tumor establishment. (2008). Am. J. Pathol. 173:  1528-1539.

Palacios G, Crawford HC,  Vaseva A and Moll UM.  Mitochondrially targeted wild-type p53 induces apoptosis in a solid human tumor xenograft model.  (2008) Cell Cycle, 7: 2584-2590

Sawey ET, Johnson JA, Crawford HC.  Matrix Metalloproteinase-7 controls pancreatic acinar cell transdifferentiation by activating the Notch signaling pathway. (2007) Proc. Natl. Acad. Sci. USA  104:19327-32.

Sawey, E.T. and Crawford HC. Metalloproteinases and cell fate: Notch just ADAMs anymore. (2008) Cell Cycle 7.

Rubin CT, Capilla E, Luu YK, Busa B, Crawford H,  Nolan DJ, Mittal V, Rosen C, Pessin JE and Judex S.  (2007).   Adipogenesis is inhibited by brief, daily exposure to high frequency, extremely low magnitude mechanical signals.  Proc. Natl. Acad. Sci USA, 104:  17879-17884.

Lynch CC, Vargo-Gogola T, Martin MD, Fingleton B, Crawford HC, Matrisian LM. (2007). Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor.  Cancer Res. 67:  6760-6767.

Kuhlmann KFD, van Till JWO, Boermeester MA, de Reuver PR, Tzvetanova ID, G. Offerhaus JA, ten Kate FJW,    Busch ORC, van Gulik TM, Gouma DJ, Crawford HC.  Evaluation of matrix metalloproteinase-7 in plasma and pancreatic juice as a biomarker for pancreatic cancer.  (2007).  Cancer Epidemiol Biomarkers Prev, 16: 886-891.

Gorden DL, Fingleton B, Crawford HC, Jansen DE, Lepage M, Matrisian LM.  (2007). Resident stromal cell-derived MMP-9 promotes the growth of colorectal metastases in the liver microenvironment.  Int J Cancer. 125:  495-500.

Fingleton B, Powell WC, Crawford HC, Couchman JR, Matrisian LM. (2007).  A rat monoclonal antibody that recognizes pro- and active MMP-7 indicates polarized expression in vivo.  Hybridoma.  26:  22-27.

Hou JC, Shigematsu S, Crawford HC, Anastasiadis PZ, Pessin JE. (2006)  Dual regulation of Rho and Rac by p120 catenin controls adipocyte plasma membrane trafficking.  J. Biol Chem. 28: 23307-23312.

Spring CM, Kelly KF, O'Kelly I, Graham M, Crawford HC, Daniel JM.  (2005).  The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin.  Exp Cell Res. 305: 253-265.

Margulis A, Zhang W, Alt-Holland A, Crawford HC, Fusenig NE, Garlick JA.  (2005).  E-cadherin suppression    accelerates squamous cell carcinoma progression in three-dimensional, human tissue constructs.  Cancer Res. 65:  1783-1791.

McCawley LJ, Crawford HC, King LE Jr, Mudgett J, Matrisian LM.  (2004).  A protective role for matrix metalloproteinase-3 in squamous cell carcinoma.  Cancer Res. 64:6965-72.

Gustavson MD, Crawford HC, Fingleton B, Matrisian LM.  (2004).  Tcf binding sequence and position determines beta-catenin and Lef-1 responsiveness of MMP-7 promoters.  Mol Carcinog. 41:125-39.

Lynch CC, Crawford HC, Matrisian LM and McDonnell SS.  (2004)  Epidermal growth factor upregulates matrix metalloproteinase-7 expression through activation of PEA3 transcription factors.  Int. J. Oncol.  24:  1565-1572.

Marchenko ND, Marchenko GN, Weinreb RN, Lindsey JD, Kyshtoobayeva A, Crawford HC, Strongin AY. b-Catenin regulates the gene of MMP-26, a novel matrix metalloproteinase expressed both in carcinomas and normal epithelial cells.  2004.  Int J Biochem Cell Biol. 36:942-56.

Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, Ross S, Conrads TP, Veenstra S, Hitt BA, Kawaguchi Y, Johann D, Liotta LA, Crawford HC, Putt ME, Jacks T, Wright CVE, Hruban RH, Lowy AM, Tuveson DA.  Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. 2003.  Cancer Cell.  4: 437-450.

Crawford HC, Krishna US, Israel DA, Matrisian LM, Washington MK, and Peek RM.  Helicobacter pylori strain-selective induction of matrix metalloproteinase-7 in vitro and within gastric mucosa.  2003.  Gastroenterology. 125: 1125-1136.

Rivat C, Le Floch N, Sabbah M, Teyrol I, Redeuilh G, Bruyneel E, Mareel M, Matrisian LM, Crawford HC, Gespach C, Attoub S.  Synergistic cooperation between the AP-1 and LEF-1 transcription factors in activation of the matrilysin promoter by the src oncogene: implications in cellular invasion.  2003.  FASEB J. 17:1721-1723.

Liu Y, Jiang H, Crawford HC, Hogan BL.  Role for ETS domain transcription factors Pea3/Erm in mouse lung development. 2003.  Dev Biol. 261:10-24.

Vargo-Gogola T, Crawford HC, Fingleton B, Matrisian LM.  Identification of novel matrix metalloproteinase-7 (matrilysin) cleavage sites in murine and human Fas ligand.  2002.  Arch Biochem Biophys. 15;408:155-61.

Vargo-Gogola T, Fingleton B, Crawford HC, Matrisian LM.  Matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo.  2002.  Cancer Res.  62:5559-5563. 

Daniel JM, Spring CM, Crawford HC, Reynolds AB, Baig A.  The p120(ctn)-binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides. 2002. Nucleic Acids Res.  30: 2911-2919.

Crawford HC, Scoggins CR, Washington MK, Matrisian LM, Leach SD.  Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas. 2002.  J Clin Invest. 109:1437-1444.

Fingleton B, Vargo-Gogola T, Crawford HC, Matrisian LM.  Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. 2001. Neoplasia  3:459-468.

Hulboy DL, Matrisian LM, Crawford HC.  Loss of JunB activity enhances stromelysin 1 expression in a model of the epithelial-to-mesenchymal transition of mouse skin tumors.  2001.  Mol Cell Biol.  21:5478-5487.

Agnihotri R, Crawford HC, Haro H, Matrisian LM, Havrda MC, Liaw L.  Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin).  2001. J Biol Chem. 276:28261-28267.

Wagenaar RA, Crawford HC, Matrisian LM.  Stabilized b-catenin immortalizes colonic epithelial cells.  2001.  Cancer Res.  61:2097-2104.

Howe LR, Crawford HC, Subbaramaiah K, Hassell JA, Dannenberg AJ, Brown AM.  PEA3 is up-regulated in response to Wnt1 and activates the expression of cyclooxygenase-2. 2001.  J Biol Chem.  276 :20108-15.

Crawford HC, Fingleton B, Gustavson MD, Kurpios N, Wagenaar RA, Hassell JA, Matrisian LM.  The PEA3 subfamily of Ets transcription factors synergizes with b-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. 2001.  Mol Cell Biol. 21:1370-1383.

Noe V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, Bruyneel E, Matrisian LM, Mareel M.  Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1.  2001.  J Cell Sci. 114:111-118.

Anastasiadis PZ, Moon SY, Thoreson MA, Mariner DJ, Crawford HC, Zheng Y, Reynolds AB.  Inhibition of RhoA by p120 catenin. 2000.  Nat Cell Biol. 2:637-644.

Fenrick R, Wang L, Nip J, Amann JM, Rooney RJ, Walker-Daniels J, Crawford HC, Hulboy DL, Kinch MS, Matrisian LM, Hiebert SW.  TEL, a putative tumor suppressor, modulates cell growth and cell morphology of ras-transformed cells while repressing the transcription of stromelysin-1.  2000.  Mol Cell Biol. 20:5828-5839.

Haro H, Crawford HC, Fingleton B, Shinomiya K, Spengler DM, Matrisian LM.  Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption  2000. J Clin Invest. 105:143-150.

Haro H, Crawford HC, Fingleton B, MacDougall JR, Shinomiya K, Spengler DM, Matrisian LM.  Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption. 2000.  J Clin Invest. 105:133-141.

Crawford HC, Fingleton BM, Rudolph-Owen LA, Goss KJ, Rubinfeld B, Polakis P, Matrisian LM.  The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. 1999. Oncogene. 18:2883-2891.

Crawford HC, Matrisian LM, Liaw L. Distinct roles of osteopontin in host defense activity and tumor survival during squamous cell carcinoma progression in vivo.  1998. Cancer Res. 58:5206-5215.

Dong Z, Crawford HC, Lavrovsky V, Taub D, Watts R, Matrisian LM, Colburn NH. A dominant negative mutant of jun blocking 12-O-tetradecanoylphorbol-13-acetate-induced invasion in mouse keratinocytes.  1997.  Mol Carcinog. 19:204-212.