Dirk Spitzer, PhD

Expertise


Specialty Areas


Translational cancer drug development, including biomarker-targeted TRAIL-based biologics and targeted, dual-domain small molecules harnessing the sigma-2 ligand/receptor interaction.

Common Diagnoses Treated


  • Pancreatic Cancer
  • Ovarian Cancer
Education


Degrees


Graduate School: PhD in Molecular Biology, Technical University Carolo-Wilhelmina zu Braunschweig, Braunschweig, Germany, 1999

Postdoctoral Education


Postdoctoral Scientist, Helmholtz Center for Infection Research, Braunschweig, Germany, 2001

Postdoctoral Scientist, Washington University School of Medicine, Department of Internal Medicine, Division of Rheumatology, St. Louis, MO, 2006

Professional Memberships


American Association for Cancer Research (AACR)

Academy of Model Aeronautics (AMA)

Siteman Cancer Center (SCC)

Society for Immunotherapy of Cancer (SITC)

Awards and Honors


2017 – Invited speaker, 13th PEGS, Essential Protein Engineering Summit, Boston, MA

2016 – Invited speaker and BuzZ Session host, 15th Annual PepTalk, The Protein Science Week, San Diego, CA

2015 – Invited speaker and chair, 11th PEGS, Essential Protein Engineering Summit, Boston, MA

2006 – Travel Fellowship Award, XXIst International Complement Workshop, Beijing, China

Featured Researcher (Missouri Researcher Spotlight), Missouri Cures

Research


Areas of Research Interest


Throughout my professional career, I have consistently pursued the translational aspects of biomedical research. I have been developing cancer therapeutics since 2007. As such, I have been involved in the design and development of two drug platform technologies based on biologics and small molecules. More specifically, I designed, patented and published on a novel form of the tumor surveillance cytokine TRAIL, designated TR3. In addition to exploring the extrinsic death pathway utilizing the TR3 biologic, I am also focusing on the targeted delivery of small molecule drugs (peptidomimetics) conjugated to sigma-2 ligands as vehicles.

Innovations


Patents:

Spitzer, D. and Hawkins, W.G. MESOTHELIN-TARGETED CANCER THERAPEUTICS WITH FULLY HUMAN scFv-TR3 FUSION PROTEINS (U.S. Provisional Application No. 62/500,377), 02. May 2017.

Hawkins, W.G., Mach, R.H., Spitzer, D. and Vangveravong, S. A dual domain small molecule drug facilitates sigma-2 mediated tumor targeting and induces ferroptosis via its effector domain erastin. (US provisional patent application, 2014).

Spitzer, D. and Hawkins, W.G. Tumor targeted TNF-related apoptosis inducing ligand fusion polypeptide, methods and uses thereof. US Patent 9,127,081, issued September 8, 2015 based on USPTO appl. 61/645,058 (WUSTL ref 011885), 2012.

Spitzer, D., Hotchkiss, R.S. and Hawkins, W.G. TRAIL timers, methods and uses thereof. US Patent 8,461,311, issued June 11, 2013 based on USPTO appl. 13/155,577 (WUSTL ref 007646-ORD1/1), 2010.

Atkinson, J.P. and Spitzer, D. Site-directed in vivo complement inhibition by soluble complement regulatory proteins containing a single chain antibody fragment as a targeting epitope. (US provisional patent application, 2004).

Wirth, D., Spitzer, D. and Hauser, H. Development of viruses resistant to inactivation by the human complement system. International Patent PCT/EP 98/07 484 based on EP 97 120 402.9, 1997.

Financial Disclosures


I am a shareholder of Accuronix Therapeutics, Inc.

Publications


Diebolder, P., Mpoy, C., ,Scott, J., Huynh, T.T., Fields, R., Spitzer, D., Bandara, N. and Rogers, B.E. PRECLINICAL EVALUATION OF AN ENGINEERED SINGLE-CHAIN FRAGMENT VARIABLE-FRAGMENT CRYSTALLIZABLE TARGETING HUMAN CD44. J. Nucl. Med. 2021 Jan;62(1):137-143. doi: 10.2967/jnumed.120.249557. Epub 2020 Jun 8.

Pati, M.L., Niso, M., Spitzer, D., Berardi, F., Contino, M., Riganti, C., Hawkins, W.G. and Abate, C. Multifunctional thiosemicarbazones and deconstructed analogues as a strategy to study the involvement of metal chelation, Sigma-2 (σ2) receptor and P-gp protein in the cytotoxic action: In vitro and in vivo activity in pancreatic tumors. Eur. J. Med. Chem. 2018 Jan 20;144:359-371. doi: 10.1016/j.ejmech.2017.12.024. Epub 2017 Dec 8.

Hashim, Y.M., Vangveravong, S., Sankpal, N.V., Binder, P.S., Liu, J., Goedegebuure, S.P., Mach, R.H., Spitzer, D. and Hawkins, W.G. The Targeted SMAC Mimetic SW IV-134 is a strong enhancer of standard chemotherapy in pancreatic cancer. J. Exp. Clin. Cancer Res.; 36:14. DOI: 10.1186/s13046-016-0470-4, 2017.

Kuroki, L.M., Jin, X., Dmitriev, I.P., Kashentseva, E.A., Powell, M.A., Mutch, D.G., Dietz, A.B., Curiel, D.T., Hawkins, W.G. and Spitzer, D. Adenovirus platform enhances transduction efficiency of human mesenchymal stem cells: An opportunity for cellular carriers of targeted TRAIL-based TR3 biologics in ovarian cancer. PLOS ONE, 2017 Dec 21;12(12):e0190125. doi: 10.1371/journal.pone.0190125. eCollection 2017.

Pati, M.L., Hornick, J.R., Niso, M., Berardi, F., Spitzer, D., Abate, C. and Hawkins, W.G. Sigma-2 receptor agonist derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1 -yl)propyl]piperazine (PB28) induce cell death via mitochondrial superoxide production and caspase activation in pancreatic cancer. BMC Cancer; 17(1):51. doi: 10.1186/s12885-016-3040-4, 2017.

Su, Y., Tatzel, K., Wang, X., Belt, B., Binder, P., Kuroki, L., Powell, M.A., Mutch, D.G., Hawkins, W.G. and Spitzer, D. Mesothelin’s minimal MUC16 binding moiety converts TR3 into a potent cancer therapeutic via hierarchical binding events at the plasma membrane. Oncotarget, doi: 10.18632/oncotarget.8925, 2016.

Ohman, K.A., Hashim, Y.M., Vangveravong, S., Nywening, T.M., Cullinan, D.R., Goedegebuure, S.P., Liu, J., Van Tine, B.A., Tiriac, H., Tuveson, D.A., DeNardo, D.G., Spitzer, D., Mach, R.H. and Hawkins, W.G. Conjugation to the sigma-2 ligand SV119 overcomes uptake blockade and converts dm-Erastin into a potent pancreatic cancer therapeutic. Oncotarget, doi: 10.18632/oncotarget.9551, 2016.

Tatzel, K., Kuroki, L., Dmitriev, I., Kashentseva, E., Curiel, D.T., Goedegebuure, S.P., Powell, M.A., Mutch, D.G., Hawkins, W.G. and Spitzer D. Membrane-proximal TRAIL species are incapable of inducing short circuit apoptosis signaling: Implications for drug development and basic cytokine biology. Sci. Rep. 6, 22661; doi: 10.1038/srep22661, 2016.

Wilkinson-Ryan, I., Kim, J., Kim, S., Dodson, L., Ferhat, A.K., Colonna, M., Swieck, M., Powell, M., Mutch, D., Spitzer, D., Hansen, T., Goedegebuure, P., Curiel, D. and Hawkins, W. Incorporation of porcine adenovirus 4 fiber protein enhances infectivity of adenovirus vector on dendritic cells: implications for immune-mediated cancer therapy. PLoS One. 2015 May 1;10(5):e0125851. doi: 10.1371/journal.pone.0125851. eCollection 2015.

Garg, G., Vangveravong, S., Zeng, Z., Collins, L., Hornick, M., Hashim, Y., Piwnica-Worms, D., Powell, M.A., Mutch, D.G., Mach, R.H., Hawkins, W.G.*, and Spitzer D.* Conjugation to a SMAC mimetic potentiates sigma-2 ligand induced tumor cell death in ovarian cancer. Mol. Cancer, Mar 7;13:50. doi: 10.1186/1476-4598-13-50, 2014.

Hashim, Y.M., Spitzer, D., Vangveravong, S., Hornick, M., Garg, G., Hornick, J.R., Goedegebuure, P., Mach, R.H. and Hawkins, W.G. Targeted pancreatic cancer therapy with the small molecule drug conjugate SW IV-134. Mol. Onc. Mar 26. pii: S1574-7891(14)00053-2. doi: 10.1016/j.molonc.2014.03.005. [Epub ahead of print], 2014.

Garg, G., Gibbs, J., Belt, B., Powell, M.A., Mutch, D.G Goedegebuure, P., Collins, L., Piwnica-Worms, D., Hawkins, W.G. and Spitzer, D. Novel treatment option for MUC16-positive malignancies with the targeted TRAIL-based fusion protein Meso-TR3. BMC Cancer, 14(1):35, 2014.

Zhong, H., Sanchez, C., Spitzer, D., Plambeck-Suess, S., Gibbs, J., Hawkins, W.G., Denardo, D., Gao, F., Pufahl, R.A., Lockhart, A.C., Xu, M., Linehan, D., Weber, J. and Wang-Gillam, A. Synergistic effects of concurrent blockade of PI3K and MEK pathways in pancreatic cancer preclinical models. PLoS One 8(10):e77243. doi: 10.1371/journal.pone.0077243, 2013.

Zaitsev, S., Kowalska, M.A., Neyman, M., Carnemolla, R., Tliba, S., Ding, B.S., Stonestrom, A., Spitzer, D., Atkinson, J.P., Poncz, M., Cines, D.B., Esmon, C.T. and Muzykantov, V.R. Targeting recombinant thrombomodulin fusion protein to red blood cells provides multifaceted thromboprophylaxis. Blood 2012 Apr 4. [Epub ahead of print]

Hornick, J.R., Vangveravong, S., Spitzer, D., Abate, C., Berardi, F., Goedegebuure, P., Mach, R.H. and Hawkins, W.G. Lysosomal Membrane Permeabilization is an Early Event in Sigma-2 Receptor Ligand Mediated Cell Deathin Pancreatic Cancer. J. Exp. & Clin. Cancer Res. 2012, 31:41 DOI:10.1186/1756-9966-31-41 Published: 2 MAY 2012.

Cheney, E.E., Wise, E.L., Bui, J.D., Schreiber, R.D., Carayannopoulos, L.N., Spitzer, D., Zafirova, B., Polic, B., Shaw, A.S. and Markiewicz, M.A. A dual function of NKG2D ligands in NK-cell activation. Eur. J. Immunol. 2012 Jun 28. doi:10.1002/eji.201141849. [Epub ahead of print]

Hornick, J.R., Spitzer, D., Goedegebuure, P., Mach, R.H. and Hawkins, W.G. Therapeutic targeting of pancreatic cancer utilizing sigma-2 ligands. Surgery 2012 Jul 2. [Epub ahead of print]

Hornick, J.R., Vangveravong, S., Spitzer, D., Abate, C., Berardi, F., Goedegebuure, P.S., Mach, R.H. and Hawkins, W.G. Lysosomal Membrane Permeabilization is an Early Event in Sigma-2 Receptor Ligand Mediated Cell Death in Pancreatic Cancer. J. Exp. & Clin. Cancer Res. 31:41, 2012.

Xu, J., Zeng, C., Chu, W., Pan, F., Rothfuss, J.M., Zhang, F., Tu, Z., Zhou, D., Zeng, D., Vangveravong, S., Johnston, F., Spitzer, D., Chang, K.C., Hotchkiss, R.H., Hawkins, W.G., Wheeler, K.T. and Mach, R.H. Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site. Nat. Commun. 2:380, 2011.

Abate, C., Hornick, J.R., Spitzer, D., Hawkins, W.G., Niso, M., Perrone, R. and Berardi, F. Fluorescent Derivatives of σ Receptor Ligand 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4- tetrahydronaphthalen-1-yl) propyl]piperazine (PB28) as a Tool for Uptake and Cellular Localization Studies in Pancreatic Tumor Cells. J. Med. Chem. 54:5858-5867, 2011.

Spitzer, D., Simon, P.O. Jr., Kashiwagi, H., Xu, J., Zeng, C., Vangveravong, S., Zhou, D., Chang, K., McDunn, J.E., Hornick, J.R., Goedegebuure, P.S., Hotchkiss, R.S., Mach, R.H. and Hawkins, W.G. Use of multifunctional sigma-2 receptor ligand conjugates to trigger cancer-selective cell death signaling. Cancer Res. 2011 Nov 7. [Epub ahead of print]

Kavanagh, D., Spitzer, D., Kothari, P., Shaikh, A., Liszewski, M.K., Richards, A., and Atkinson, J.P. New roles for the major human 3′-5′ exonuclease TREX1 in human disease. Cell Cycle 7:1718-1725, 2008.

Wu, X., Spitzer, D., Mao, D., Peng, S.L., Molina, H. and Atkinson, J.P. Membrane protein Crry maintains homeostasis of the complement system. J. Immunol. 181, 2732-2740, 2008.

Kavanagh, D., Burgess, R., Spitzer, D., Richards, A., Dias-Torres, M.L., Goodship, J.A., Hourcade, D.E., Atkinson, J.P. and Goodship, T.H.J. The decay accelerating factor mutation I197V found in hemolytic uraemic syndrome does not impair complement regulation. Mol. Immunol., 44, 3162-3167, 2007.

Spitzer, D., Mitchell L.M., Atkinson, J.P. and Hourcade, D.E. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J. Immunol. 179, 2600-2608, 2007.

Kavanagh, D., Burgess, R., Spitzer, D., Richards, A., Dias-Torres, M.L., Goodship, J.A., Hourcade, D.E., Atkinson, J.P. and Goodship, T.H.J. The decay accelerating factor mutation I197V found in hemolytic uraemic syndrome does not impair complement regulation. Mol. Immunol., 44, 3162-3167, 2007.

Spitzer, D., Mitchell L.M., Atkinson, J.P. and Hourcade, D.E. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J. Immunol. 179, 2600-2608, 2007.

Richards, A., Kavanagh, D., Jen, J., van den Maagdenberg, A.M.J.M., Bertram, P., Spitzer, D., et al., C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat. Genet. 39, 1068-1070, 2007.

Spitzer, D., Wu, X., Ma, X., Xu, L., Ponder, K.P. and Atkinson, J.P. Cutting edge: Treatment of complement regulatory protein deficiency by in vivo gene therapy. J. Immunol., 177, 4953-4956, 2006.

Gill D.B., Spitzer, D., Koomey, M., Heuser, J.E. and Atkinson, J.P. Release of host-derived membrane vesicles following pilus-mediated adhesion of Neisseria gonorrhoeae. Cell. Microbiol. 7, 1672-1683, 2005.

Spitzer, D., Unsinger, J., Mao, D., Wu, X., Molina, H. and Atkinson, J.P. In vivo correction of complement regulatory protein deficiency with an inhibitor targeting the red blood cell membrane. J. Immunol. 175, 7763-7770, 2005.

Spitzer, D., Unsinger, J., Bessler, M. and Atkinson, J.P. ScFv-mediated in vivo targeting of DAF to erythrocytes inhibits lysis by complement. Mol. Immunol. 40, 911-919, 2004.

Weissenbach, M., Weber, C., Spitzer, D., Wirth, D., Heinrich, P.C. and Schaper, F. Interleukin-6 is a direct mediator of T cell migration. Eur. J. Immunol. 34, 2895-2906, 2004.

Spitzer, D., Dittmar, K.E.J., Rohde, M., Hauser, H. and Wirth, D. Green fluorescent protein-tagged retroviral envelope protein for analysis of virus-cell interactions. J. Virol. 77, 6070-6075, 2003.

MacLeod, R.A.F., Spitzer, D., Bar-Am, I., Gosden, J., Kaufmann, M. and Drexler, H.G. Karyotypic dissection of Hodgkin’s disease cell lines reveals ectopic subtelomers and ribosomal DNA at sites of multiple jumping translocations and genomic amplification. Leukemia 14, 1803-1814, 2000.

Hauser, H., Spitzer, D., Verhoeyen, E., Unsinger, J. and Wirth, D. New approaches towards ex vivo and in vivo gene therapy. Cells, Tissues, Organs 167, 75-80, 2000.

Spitzer, D., Hauser, H. and Wirth, D. Complement protected amphotropic retroviruses from murine packaging cells. Hum. Gene Ther. 10, 1893-1902, 1999.

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