MENU

Matthew K. Robinson, PhD

Matthew Robinson, PhD
About

Assistant Professor

Research Program

Crystal structure (2.4 Å) of the F4 anti-ErbB3 Fab
Combination of two anti-ErbB3 mAbs (A5/F4) more effectively blocks signaling downstream of the ErbB3 receptor and synergizes with other ErbB-targeted agents to improve cancer cell killing
Figure 3
Figure 4
18 F bone scan of severe combined immunodeficienct (SCID) mouse
18F-FLT-PET imaging of human tumor xenografts in SCID mice
Imaging with the anti-HER2 diabody is antigen-dependent.
ALM binds to and blocks function of both ErbB2 and ErbB3. Test
Education, Training & Credentials

Educational Background

  • Postdoctoral fellow, Genetics Department, Yale University of School of Medicine
  • PhD, Genetics, University of Rochester, 1997
  • MS, Biochemistry, University of Rochester, 1994

Memberships

  • American Association for Cancer Research
  • The Antibody Society
  • American Association of Pharmaceutical Scientists (member: Pharmacoimaging Steering committee)

Honors & Awards

  • American Cancer Society “Meet the Professors” invitee, 2009
  • Thermo Scientific-ABRF Outstanding Scientist Award, 2009
  • Wallace O. Fenn Award for Outstanding Thesis at School of Medicine and Dentistry, 1997
Research Profile

Research Program

Research Interests

Antibody-based agents for the detection and treatment of cancer

  • Exploiting protein–engineering strategies to optimize efficacy of antibody-based agents
  • Dissecting mechanisms of resistance to antibody-based therapies
  • Antibody-based imaging of cancer to improve detection and treatment

 

Lab Overview

Antibodies represent an important class of targeted cancer therapies. While antibody-based therapies show efficacy against a variety of cancer types they, like targeted therapies in general, often suffer from the problem of drug resistance. The Robinson laboratory is taking two distinct, but complimentary, approaches to improve the efficacy of antibody-based therapies. The first is a direct approach of developing and implementing antibody-engineering techniques to rationally design and build antibodies with improved function. Second, we are interested in identifying the mechanisms of action associated with antibodies and determining the molecular basis by which cancer cells develop resistance to those agents.

The majority of our work focuses on the ErbB receptor tyrosine kinase family (EGFR, ErbB2/HER2, ErbB3/HER3, & ErbB4/HER4). Inappropriate activation of these receptors drives cancer formation and progression in a number of tissues. Overexpression of these proteins, as seen in ErbB2+ Breast and gastric cancers and EGFR+ head and neck cancer, correlates with aggressive disease and poor patient outcomes. This has led to the development of agents that are capable of blocking signaling through those receptors and improving patient outcomes. ErbB3, understudied as a drug target in comparison to EGFR and ErbB2, is increasingly recognized as a driver of resistance to ErbB-targeted therapies. Projects in the laboratory are focused on developing both ErbB3-targeted therapies and strategies to effectively exploit the therapeutic activity of those agents. We have also used high throughput screening approaches to identify novel components of signaling networks downstream of the ErbB receptor tyrosine kinases. Work is ongoing to understand how those proteins function within ErbB signaling networks and how those interactions can lead to drug resistance. The ultimate goal of this work is to identify treatment strategies that exploit those interactions to overcome resistance.

People

Irina Shchaveleva, MS

Scientific Technician II

Room: W322
215-728-3648
Publications

Selected Publications

Lehmann, A.♯, Wixted, J.H.F.♯, Shapovalov, M.V., Roder, H., Dunbrack, R.L.*, Robinson, M.K.*. Stability engineering of anti-EGFR scFv antibodies by rational design of a lambda-to-kappa swap of the VL framework using a structure-guided approach. MAbs. 2015 Sep 4:0. [Epub ahead of print] PubMed PMID: 26337947. ♯ = contributed equally, * = co-corresponding authors PubMed

Ramirez, U.D., Nikonova, A.S., Liu, H., Pecherskaya, A., Lawrence, S.H., Serebriiskii, I.G., Zhou, Y., Robinson, M.K., Einarson, M.B., Golemis, E.A., Jaffe, E.K. Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization. BMC Cancer 15:436, 2015. PMCID: PMC4451962. PubMed

Burns, K., Robinson, M.K., Thévenin, D. Inhibition of Cancer Cell Proliferation and Breast Tumor Targeting of pHLIP-Monomethyl Auristatin E Conjugates. Mol Pharm 12:1250-1258, 2015. PMCID: PMC4476257. PubMed

D'Souza, J.W., Reddy, S., Goldsmith, L.E., Shchaveleva, I., Marks, J.D., Litwin, S., Robinson, M.K. Combining anti-ERBB3 antibodies specific for domain I and domain III enhances the anti-tumor activity over the individual monoclonal antibodies. PLoS ONE 9: e112376, 2014. PMCID: PMC4227695. PubMed

Lerner, M., D'Souza, J., Pazina, T., Dailey, J., Goldsmith, B., Robinson, M.K.*, Johnson, A.T.* Hybrids of a genetically engineered antibody and a carbon nanotube transistor for detection of prostate cancer biomarkers. ACS Nano 6:5143-5149, 2012. PubMed

Miller, J., Doss, M., McQuillen, R., Shaller, C.C., Tolner, B., Yu, J.Q., Chester, K., Robinson, M.K. Impact of expression system on the function of the C6.5 diabody PET radiotracer. Tumor Biology 33:617-27, 2012. PMCID:PMC3761356. PubMed

Loo, L., Capobianco, J.A., Wei, W., Gao, X., Shih, W.Y., Shih, W-H., Pourrezaei, K., Robinson, M.K., Gregory P. Adams, G.P. Highly sensitive detection of HER2 extracellular domain (ECD) in the serum of breast cancer patients by piezoelectric microcantilevers (PEMS). Anal Chem., 83(9):3392-3397, 2011. PMCID: PMC3084889. PubMed

Reddy, S, Shaller, C.C., Doss, M., Shchaveleva, I., Marks, J.D., Yu, J.Q., Robinson, M.K. Evaluation of the anti-HER2 C6.5 diabody as a PET radiotracer to monitor HER2 status and predict response to trastuzumab treatment. Clin Cancer Res, 17:1509-1520, 2011. PMCID: PMC3060271. PubMed

Robinson, M.K., Hodge, K.M., Horak, E., Sundberg, Å.L., Russeva, M., Shaller, C.C., Simmons, H.H., von Mehren, M., Shchaveleva, I., Marks, J.D., Adams, G.P. Targeting ErbB2 and ErbB3 with a Bispecific-Single Chain Fv Enhances Targeting Selectivity and Induces a Therapeutic Effect in vitro. Br J Cancer 99:1415-1425, 2008. PMCID: PMC2576487. PubMed

Zhang, J., Valianou, M., Simmons, H., Robinson, M.K., Lee, H.O., Mullins, S.R., Marasco, W.A., Adams, G.P., Weiner, L.M., Cheng, J.D. Identification of inhibitory scFv antibodies targeting fibroblast activation protein utilizing phage display functional screens. FASEB J epublication date: October 30, 2012. PMC Journal – In Process. PubMed

Lerner, M., D'Souza, J., Pazina, T., Dailey, J., Goldsmith, B., Robinson, M.K.*, Johnson, A.T.* Hybrids of a genetically engineered antibody and a carbon nanotube transistor for detection of prostate cancer biomarkers. ACS Nano 6:5143-5149, 2012. PMCID: PMC3383883 * = co-corresponding authors. PubMed

Miller, J., Doss, M., McQuillen, R., Shaller, C.C., Tolner, B., Yu, J.Q., Chester, K., Robinson, M.K. Impact of expression system on the function of the C6.5 diabody PET radiotracer. Tumor Biology 33:617-27, 2012. PMC Journal – In Process. PubMed

Reddy, S, Shaller, C.C., Doss, M., Shchaveleva, I., Marks, J.D., Yu, J.Q., Robinson, M.K. Evaluation of the anti-HER2 C6.5 diabody as a PET radiotracer to monitor HER2 status and predict response to trastuzumab treatment. Clin Cancer Res, 17:1509-1520, 2011. PMCID: PMC3060271. PubMed

Mehra, R., Serebriiskii, I.G., Dunbrack, R.L., Jr, Robinson, M.K., Burtness, B., Golemis, E.A.. Protein-intrinsic and signaling network-based sources of resistance to EGFR- and ErbB family-targeted therapies in head and neck cancer. Drug Resist Updat. 14: 260-279, 2011. PMCID: PMC3195944. PubMed

Reddy S, Robinson MK, Immuno-Positron Emission Tomography in Cancer Models. Semin Nucl Med. 2010 May 40:182-189. PMCID: PMC2848398 Epub 2010 Mar 31. PubMed

Additional Publications

My NCBI