Luis Alberto Diaz, MD

Research Summary

My goal is to combine world-class basic science research with clinical knowledge to produce novel diagnostic, predictive and therapeutic agents for cancer patients. My area of concentration in the laboratory has been in the preclinical development of the concept of COBALT (Combination Bacteriolytic Therapy) as well as in the development of a clinical protocol for testing this concept. I have focused on the preclinical development of COBALT and am involved in the development of future therapeutic agents from the Vogelstein/Kinzler Laboratories.

Journal Citations

Bettegowda, C.; Huang, X.; Lin, J.; Cheong, I.; Kohli, M.; Szabo, S.A.; Zhang, X.; Diaz, L.A., Jr.; Velculescu, V.E.; Parmigiani, G.; Kinzler, K.W.; Vogelstein, B.; Zhou, S. The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT. Nat Biotechnol. 2006 Nov 19;24:1573-1580.

Cheong, I.; Huang, X.; Bettegowda, C.; Diaz, L.A., Jr.; Kinzler, K.W.; Zhou, S.; Vogelstein, B. A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science. 2006 Nov 24;314(5803):1308-1311.

Cummins, J.M.; He, Y.; Leary, R.J.; Pagliarini, R.; Diaz, L.A., Jr.; Sjoblom, T.; Barad, O.; Bentwich, Z.; Szafranska, A.E.; Labourier, E.; Raymond, C.K.; Roberts, B.S.; Juhl, H.; Kinzler, K.W.; Vogelstein, B.; Velculescu, V.E. The colorectal microRNAome. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3687-3692.

Xu, J.; Sauvageot, J.; Ewing, C.M.; Sun, J.; Liu, W.; Isaacs, S.D.; Wiley, K.E.; Diaz, L.; Zheng, S.L.; Walsh, P.C.; Isaacs, W.B. Germline ATBF1 mutations and prostate cancer risk. Prostate. 2006 Jul 1;66(10):1082-1085.

Cheong, I.; Huang, X.; Thornton, K.; Diaz, L.A., Jr.; Zhou, S. Targeting cancer with bugs and liposomes: ready, aim, fire. Cancer Res. 2007 Oct 15;67(20):9605-9608.

Diaz, L.A., Jr.; Foss, C.A.; Thornton, K.; Nimmagadda, S.; Endres, C.J.; Uzuner, O.; Seyler, T.M.; Ulrich, S.D.; Conway, J.; Bettegowda, C.; Agrawal, N.; Cheong, I.; Zhang, X.; Ladenson, P.W.; Vogelstein, B.N.; Mont, M.A.; Zhou, S.; Kinzler, K.W.; Vogelstein, B.; Pomper, M.G. Imaging of musculoskeletal bacterial infections by [124I]FIAU-PET/CT. PLoS One. 2007;2(10):e1007.

Donawho, C.K.; Luo, Y.; Luo, Y.; Penning, T.D.; Bauch, J.L.; Bouska, J.J.; Bontcheva-Diaz, V.D.; Cox, B.F.; DeWeese, T.L.; Dillehay, L.E.; Ferguson, D.C.; Ghoreishi-Haack, N.S.; Grimm, D.R.; Guan, R.; Han, E.K.; Holley-Shanks, R.R.; Hristov, B.; Idler, K.B.; Jarvis, K.; Johnson, E.F.; Kleinberg, L.R.; Klinghofer, V.; Lasko, L.M.; Liu, X.; Marsh, K.C.; McGonigal, T.P.; Meulbroek, J.A.; Olson, A.M.; Palma, J.P.; Rodriguez, L.E.; Shi, Y.; Stavropoulos, J.A.; Tsurutani, A.C.; Zhu, G.D.; Rosenberg, S.H.; Giranda, V.L.; Frost, D.J. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clinical cancer research : an official journal of the American Association for Cancer Research. 2007 May 1;13(9):2728-2737.

Peddibhotla, S.; Dang, Y.; Liu, J.O.; Romo, D. Simultaneous arming and structure/activity studies of natural products employing O-H insertions: an expedient and versatile strategy for natural products-based chemical genetics. J Am Chem Soc. 2007 Oct 10;129(40):12222-12231.

Diehl, F.; Schmidt, K.; Choti, M.A.; Romans, K.; Goodman, S.; Li, M.; Thornton, K.; Agrawal, N.; Sokoll, L.; Szabo, S.A.; Kinzler, K.W.; Vogelstein, B.; Diaz, L.A., Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008 Sep;14(9):985-990.

Dowd, K.A.; Hershow, R.C.; Yawetz, S.; Larussa, P.; Diaz, C.; Landesman, S.H.; Paul, M.E.; Read, J.S.; Lu, M.; Thomas, D.L.; Netski, D.M.; Ray, S.C. Maternal neutralizing antibody and transmission of hepatitis C virus to infants. J Infect Dis. 2008 Dec 1;198(11):1651-1655.

Herman, J.M.; Swartz, M.J.; Hsu, C.C.; Winter, J.; Pawlik, T.M.; Sugar, E.; Robinson, R.; Laheru, D.A.; Jaffee, E.; Hruban, R.H.; Campbell, K.A.; Wolfgang, C.L.; Asrari, F.; Donehower, R.; Hidalgo, M.; Diaz, L.A., Jr.; Yeo, C.; Cameron, J.L.; Schulick, R.D.; Abrams, R. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol. 2008 Jul 20;26(21):3503-3510.

Hermes, G.; Ajioka, J.W.; Kelly, K.A.; Mui, E.; Roberts, F.; Kasza, K.; Mayr, T.; Kirisits, M.J.; Wollmann, R.; Ferguson, D.J.; Roberts, C.W.; Hwang, J.H.; Trendler, T.; Kennan, R.P.; Suzuki, Y.; Reardon, C.; Hickey, W.F.; Chen, L.; McLeod, R. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection. Journal of neuroinflammation. 2008;5:48.

McLerran, D.; Grizzle, W.E.; Feng, Z.; Bigbee, W.L.; Banez, L.L.; Cazares, L.H.; Chan, D.W.; Diaz, J.; Izbicka, E.; Kagan, J.; Malehorn, D.E.; Malik, G.; Oelschlager, D.; Partin, A.; Randolph, T.; Rosenzweig, N.; Srivastava, S.; Srivastava, S.; Thompson, I.M.; Thornquist, M.; Troyer, D.; Yasui, Y.; Zhang, Z.; Zhu, L.; Semmes, O.J. Analytical Validation of Serum Proteomic Profiling for Diagnosis of Prostate Cancer: Sources of Sample Bias. Clin Chem. 2008 Jan;54(1):44-52.

McLerran, D.; Grizzle, W.E.; Feng, Z.; Thompson, I.M.; Bigbee, W.L.; Cazares, L.H.; Chan, D.W.; Dahlgren, J.; Diaz, J.; Kagan, J.; Lin, D.W.; Malik, G.; Oelschlager, D.; Partin, A.; Randolph, T.W.; Sokoll, L.; Srivastava, S.; Srivastava, S.; Thornquist, M.; Troyer, D.; Wright, G.L.; Zhang, Z.; Zhu, L.; Semmes, O.J. SELDI-TOF MS Whole Serum Proteomic Profiling with IMAC Surface Does Not Reliably Detect Prostate Cancer. Clin Chem. 2008 Jan;54(1):53-60.

Parsons, D.W.; Jones, S.; Zhang, X.; Lin, J.C.; Leary, R.J.; Angenendt, P.; Mankoo, P.; Carter, H.; Siu, I.M.; Gallia, G.L.; Olivi, A.; McLendon, R.; Rasheed, B.A.; Keir, S.; Nikolskaya, T.; Nikolsky, Y.; Busam, D.A.; Tekleab, H.; Diaz, L.A., Jr.; Hartigan, J.; Smith, D.R.; Strausberg, R.L.; Marie, S.K.; Shinjo, S.M.; Yan, H.; Riggins, G.J.; Bigner, D.D.; Karchin, R.; Papadopoulos, N.; Parmigiani, G.; Vogelstein, B.; Velculescu, V.E.; Kinzler, K.W. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008 Sep 26;321(5897):1807-1812.

Diaz, L.A., Jr.; Messersmith, W.; Sokoll, L.; Sinibaldi, V.; Moore, S.; Carducci, M.; Eisenberger, M. TNF-blockade in patients with advanced hormone refractory prostate cancer. Invest New Drugs. 2009 Oct 21.
Grossman, S.A.; Ye, X.; Chamberlain, M.; Mikkelsen, T.; Batchelor, T.; Desideri, S.; Piantadosi, S.; Fisher, J.; Fine, H.A. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol. 2009 Sep 1;27(25):4155-4161.

Li, M.; Chen, W.D.; Papadopoulos, N.; Goodman, S.N.; Bjerregaard, N.C.; Laurberg, S.; Levin, B.; Juhl, H.; Arber, N.; Moinova, H.; Durkee, K.; Schmidt, K.; He, Y.; Diehl, F.; Velculescu, V.E.; Zhou, S.; Diaz, L.A., Jr.; Kinzler, K.W.; Markowitz, S.D.; Vogelstein, B. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009 Sep;27(9):858-863.

Sur, S.; Pagliarini, R.; Bunz, F.; Rago, C.; Diaz, L.A., Jr.; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N. A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53. Proc Natl Acad Sci U S A. 2009;106(10):3964-3969.

Yun, J.; Rago, C.; Cheong, I.; Pagliarini, R.; Angenendt, P.; Rajagopalan, H.; Schmidt, K.; Willson, J.K.; Markowitz, S.; Zhou, S.; Diaz, L.A., Jr.; Velculescu, V.E.; Lengauer, C.; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 2009 Sep 18;325(5947):1555-1559.

Diaz R, J.J., Morales-Paliza M, Koehler E, Phillips J, Stinson S, Gilbert J, Chung CH, Murphy B, Yarbrough W, Murphy P, Shyr Y, Cmelak A. . Hypothyroidism as a consequence of Intensity-Modulated Radiation Therapy with concurrent Taxane-based chemotherapy for locally-advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010;77(2):468-477.

Grossman, S.A.; Ye, X.; Piantadosi, S.; Desideri, S.; Nabors, L.B.; Rosenfeld, M.; Fisher, J.; Consortium, N.C. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clinical cancer research : an official journal of the American Association for Cancer Research. 2010;16(8):2443-2449.

He, Y.; Wu, J.; Dressman, D.C.; Iacobuzio-Donahue, C.; Markowitz, S.D.; Velculescu, V.E.; Diaz, L.A., Jr.; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N. Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature. 2010 Mar 25;464(7288):610-614.

Hudson, T.J.; Anderson, W.; Artez, A.; Barker, A.D.; Bell, C.; Bernabe, R.R.; Bhan, M.K.; Calvo, F.; Eerola, I.; Gerhard, D.S.; Guttmacher, A.; Guyer, M.; Hemsley, F.M.; Jennings, J.L.; Kerr, D.; Klatt, P.; Kolar, P.; Kusada, J.; Lane, D.P.; Laplace, F.; Youyong, L.; Nettekoven, G.; Ozenberger, B.; Peterson, J.; Rao, T.S.; Remacle, J.; Schafer, A.J.; Shibata, T.; Stratton, M.R.; Vockley, J.G.; Watanabe, K.; Yang, H.; Yuen, M.M.; Knoppers, B.M.; Bobrow, M.; Cambon-Thomsen, A.; Dressler, L.G.; Dyke, S.O.; Joly, Y.; Kato, K.; Kennedy, K.L.; Nicolas, P.; Parker, M.J.; Rial-Sebbag, E.; Romeo-Casabona, C.M.; Shaw, K.M.; Wallace, S.; Wiesner, G.L.; Zeps, N.; Lichter, P.; Biankin, A.V.; Chabannon, C.; Chin, L.; Clement, B.; de Alava, E.; Degos, F.; Ferguson, M.L.; Geary, P.; Hayes, D.N.; Johns, A.L.; Kasprzyk, A.; Nakagawa, H.; Penny, R.; Piris, M.A.; Sarin, R.; Scarpa, A.; van de Vijver, M.; Futreal, P.A.; Aburatani, H.; Bayes, M.; Botwell, D.D.; Campbell, P.J.; Estivill, X.; Grimmond, S.M.; Gut, I.; Hirst, M.; Lopez-Otin, C.; Majumder, P.; Marra, M.; McPherson, J.D.; Ning, Z.; Puente, X.S.; Ruan, Y.; Stunnenberg, H.G.; Swerdlow, H.; Velculescu, V.E.; Wilson, R.K.; Xue, H.H.; Yang, L.; Spellman, P.T.; Bader, G.D.; Boutros, P.C.; Flicek, P.; Getz, G.; Guigo, R.; Guo, G.; Haussler, D.; Heath, S.; Hubbard, T.J.; Jiang, T.; Jones, S.M.; Li, Q.; Lopez-Bigas, N.; Luo, R.; Muthuswamy, L.; Ouellette, B.F.; Pearson, J.V.; Quesada, V.; Raphael, B.J.; Sander, C.; Speed, T.P.; Stein, L.D.; Stuart, J.M.; Teague, J.W.; Totoki, Y.; Tsunoda, T.; Valencia, A.; Wheeler, D.A.; Wu, H.; Zhao, S.; Zhou, G.; Lathrop, M.; Thomas, G.; Yoshida, T.; Axton, M.; Gunter, C.; Miller, L.J.; Zhang, J.; Haider, S.A.; Wang, J.; Yung, C.K.; Cross, A.; Liang, Y.; Gnaneshan, S.; Guberman, J.; Hsu, J.; Chalmers, D.R.; Hasel, K.W.; Kaan, T.S.; Lowrance, W.W.; Masui, T.; Rodriguez, L.L.; Vergely, C.; Bowtell, D.D.; Cloonan, N.; deFazio, A.; Eshleman, J.R.; Etemadmoghadam, D.; Gardiner, B.A.; Kench, J.G.; Sutherland, R.L.; Tempero, M.A.; Waddell, N.J.; Wilson, P.J.; Gallinger, S.; Tsao, M.S.; Shaw, P.A.; Petersen, G.M.; Mukhopadhyay, D.; DePinho, R.A.; Thayer, S.; Shazand, K.; Beck, T.; Sam, M.; Timms, L.; Ballin, V.; Lu, Y.; Ji, J.; Zhang, X.; Chen, F.; Hu, X.; Yang, Q.; Tian, G.; Zhang, L.; Xing, X.; Li, X.; Zhu, Z.; Yu, Y.; Yu, J.; Tost, J.; Brennan, P.; Holcatova, I.; Zaridze, D.; Brazma, A.; Egevard, L.; Prokhortchouk, E.; Banks, R.E.; Uhlen, M.; Viksna, J.; Ponten, F.; Skryabin, K.; Birney, E.; Borg, A.; Borresen-Dale, A.L.; Caldas, C.; Foekens, J.A.; Martin, S.; Reis-Filho, J.S.; Richardson, A.L.; Sotiriou, C.; Thoms, G.; van't Veer, L.; Birnbaum, D.; Blanche, H.; Boucher, P.; Boyault, S.; Masson-Jacquemier, J.D.; Pauporte, I.; Pivot, X.; Vincent-Salomon, A.; Tabone, E.; Theillet, C.; Treilleux, I.; Bioulac-Sage, P.; Decaens, T.; Franco, D.; Gut, M.; Samuel, D.; Zucman-Rossi, J.; Eils, R.; Brors, B.; Korbel, J.O.; Korshunov, A.; Landgraf, P.; Lehrach, H.; Pfister, S.; Radlwimmer, B.; Reifenberger, G.; Taylor, M.D.; von Kalle, C.; Majumder, P.P.; Pederzoli, P.; Lawlor, R.A.; Delledonne, M.; Bardelli, A.; Gress, T.; Klimstra, D.; Zamboni, G.; Nakamura, Y.; Miyano, S.; Fujimoto, A.; Campo, E.; de Sanjose, S.; Montserrat, E.; Gonzalez-Diaz, M.; Jares, P.; Himmelbaue, H.; Bea, S.; Aparicio, S.; Easton, D.F.; Collins, F.S.; Compton, C.C.; Lander, E.S.; Burke, W.; Green, A.R.; Hamilton, S.R.; Kallioniemi, O.P.; Ley, T.J.; Liu, E.T.; Wainwright, B.J. International network of cancer genome projects. Nature. 2010 Apr 15;464(7291):993-998.

Jones, S.; Wang, T.L.; Shih Ie, M.; Mao, T.L.; Nakayama, K.; Roden, R.; Glas, R.; Slamon, D.; Diaz, L.A., Jr.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E.; Papadopoulos, N. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010 Oct 8;330(6001):228-231

Karanam, B.; Peng, S.; Li, T.; Buck, C.; Day, P.M.; Roden, R.B. Papillomavirus infection requires gamma secretase. J Virol. 2010 Oct;84(20):10661-10670.

Klamerus, J.F.; Bruinooge, S.S.; Ye, X.; Klamerus, M.L.; Damron, D.; Lansey, D.; Lowery, J.C.; Diaz, L.A., Jr.; Ford, J.G.; Kanarek, N.; Rudin, C.M. The impact of insurance on access to cancer clinical trials at a comprehensive cancer center. Clin Cancer Res. 2010 Dec 15;16(24):5997-6003.

Leary, R.J.; Kinde, I.; Diehl, F.; Schmidt, K.; Clouser, C.; Duncan, C.; Antipova, A.; Lee, C.; McKernan, K.; De La Vega, F.M.; Kinzler, K.W.; Vogelstein, B.; Diaz, L.A., Jr.; Velculescu, V.E. Development of personalized tumor biomarkers using massively parallel sequencing. Sci Transl Med. 2010 Feb 24;2(20):20ra14.

Seltzer, M.J.; Bennett, B.D.; Joshi, A.D.; Gao, P.; Thomas, A.G.; Ferraris, D.V.; Tsukamoto, T.; Rojas, C.J.; Slusher, B.S.; Rabinowitz, J.D.; Dang, C.V.; Riggins, G.J. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 2010 Nov 15;70(22):8981-8987.

van Vledder, M.G.; de Jong, M.C.; Pawlik, T.M.; Schulick, R.D.; Diaz, L.A.; Choti, M.A. Disappearing colorectal liver metastases after chemotherapy: should we be concerned? J Gastrointest Surg. 2010 Nov;14(11):1691-1700.

Jiao, Y.; Shi, C.; Edil, B.H.; de Wilde, R.F.; Klimstra, D.S.; Maitra, A.; Schulick, R.D.; Tang, L.H.; Wolfgang, C.L.; Choti, M.A.; Velculescu, V.E.; Diaz, L.A., Jr.; Vogelstein, B.; Kinzler, K.W.; Hruban, R.H.; Papadopoulos, N. DAXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors. Science. 2011 Jan 20;In Press.