Charles Hart, PhD

Executive Director

Catalyst

+1 415 514-8510

Charles Hart is the director of the Catalyst program. From 2004 to 2017 he was at Threshold Pharmaceuticals and responsible for both in vitro and in vivo preclinical translational studies. He was also project leader for the global clinical development program for the hypoxia-targeted anticancer drug evofosfamide (TH-302), a partnership with Merck KGaA. Prior to joining Threshold, Charles was Senior Director of Biology at Galileo Pharmaceuticals (2001 to 2004), Director of Drug Discovery at Signature Bioscience (2000 to 2001), and a Research Unit Director at Affymax (1990 to 2000). Charles received his AB in cell biology from the University of California, Berkeley in 1977, an MS in developmental biology from Stanford University in 1980, a PhD in molecular biology and genetics from Yale University in 1987, and completed a postdoctoral fellowship at the University of Strasbourg, France in 1990.

Publications:

Retraction: Multimodal targeting of tumor vasculature and cancer stem-like cells in sarcomas with VEGF-A inhibition, HIF-1α inhibition, and hypoxia-activated chemotherapy.

Oncotarget

Yoon C, Chang KK, Lee JH, Tap WD, Hart CP, Simon MC, Yoon SS

Evofosfamide for the treatment of human papillomavirus-negative head and neck squamous cell carcinoma.

JCI insight

Jamieson SM, Tsai P, Kondratyev MK, Budhani P, Liu A, Senzer NN, Chiorean EG, Jalal SI, Nemunaitis JJ, Kee D, Shome A, Wong WW, Li D, Poonawala-Lohani N, Kakadia PM, Knowlton NS, Lynch CR, Hong CR, Lee TW, Gr?nman RA, Caporiccio L, McKee TD, Zaidi M, Butt S, Macann AM, McIvor NP, Chaplin JM, Hicks KO, Bohlander SK, Wouters BG, Hart CP, Print CG, Wilson WR, Curran MA, Hunter FW

Functional CRISPR and shRNA Screens Identify Involvement of Mitochondrial Electron Transport in the Activation of Evofosfamide.

Molecular pharmacology

Hunter FW, Devaux JBL, Meng F, Hong CR, Khan A, Tsai P, Ketela TW, Sharma I, Kakadia PM, Marastoni S, Shalev Z, Hickey AJR, Print CG, Bohlander SK, Hart CP, Wouters BG, Wilson WR

Evofosfamide for the treatment of human papillomavirus-negative head and neck squamous cell carcinoma.

JCI insight

Jamieson SM, Tsai P, Kondratyev MK, Budhani P, Liu A, Senzer NN, Chiorean EG, Jalal SI, Nemunaitis JJ, Kee D, Shome A, Wong WW, Li D, Poonawala-Lohani N, Kakadia PM, Knowlton NS, Lynch CR, Hong CR, Lee TW, Grénman RA, Caporiccio L, McKee TD, Zaidi M, Butt S, Macann AM, McIvor NP, Chaplin JM, Hicks KO, Bohlander SK, Wouters BG, Hart CP, Print CG, Wilson WR, Curran MA, Hunter FW

Hypoxia Activated Evofosfamide for Treatment of Recurrent Bevacizumab-Refractory Glioblastoma: A phase I surgical study.

Neuro-oncology

Brenner A, Zuniga R, Sun JD, Floyd J, Hart CP, Kroll S, Fichtel L, Cavazos D, Caflisch L, Gruslova A, Lodi A, Tiziani S

Hypoxia-Targeting Drug Evofosfamide (TH-302) Enhances Sunitinib Activity in Neuroblastoma Xenograft Models.

Translational oncology

Kumar S, Sun JD, Zhang L, Mokhtari RB, Wu B, Meng F, Liu Q, Bhupathi D, Wang Y, Yeger H, Hart C, Baruchel S

Metabolic and Physiologic Imaging Biomarkers of the Tumor Microenvironment Predict Treatment Outcome with Radiation or a Hypoxia-Activated Prodrug in Mice.

Cancer research

Matsumoto S, Kishimoto S, Saito K, Takakusagi Y, Munasinghe JP, Devasahayam N, Hart CP, Gillies RJ, Mitchell JB, Krishna MC

Radiotherapy Synergizes with the Hypoxia-Activated Prodrug Evofosfamide: In Vitro and In Vivo Studies.

Antioxidants & redox signaling

Takakusagi Y, Kishimoto S, Naz S, Matsumoto S, Saito K, Hart CP, Mitchell JB, Krishna MC

A Combination of Radiation and the Hypoxia-Activated Prodrug Evofosfamide (TH-302) is Efficacious against a Human Orthotopic Pancreatic Tumor Model.

Translational oncology

Hajj C, Russell J, Hart CP, Goodman KA, Lowery MA, Haimovitz-Friedman A, Deasy JO, Humm JL

Hypoxia Imaging With PET Correlates With Antitumor Activity of the Hypoxia-Activated Prodrug Evofosfamide (TH-302) in Rodent Glioma Models.

Tomography : a journal for imaging research

Stokes AM, Hart CP, Quarles CC

Preclinical Benefit of Hypoxia-Activated Intra-arterial Therapy with Evofosfamide in Liver Cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

Duran R, Mirpour S, Pekurovsky V, Ganapathy-Kanniappan S, Brayton CF, Cornish TC, Gorodetski B, Reyes J, Chapiro J, Schernthaner RE, Frangakis C, Lin M, Sun JD, Hart CP, Geschwind JF

Multimodal targeting of tumor vasculature and cancer stem-like cells in sarcomas with VEGF-A inhibition, HIF-1a inhibition, and hypoxia-activated chemotherapy.

Oncotarget

Yoon C, Chang KK, Lee JH, Tap WD, Hart CP, Simon MC, Yoon SS

MR Imaging Biomarkers to Monitor Early Response to Hypoxia-Activated Prodrug TH-302 in Pancreatic Cancer Xenografts.

PloS one

Zhang X, Wojtkowiak JW, Martinez GV, Cornnell HH, Hart CP, Baker AF, Gillies R

Comparison of hypoxia-activated prodrug evofosfamide (TH-302) and ifosfamide in preclinical non-small cell lung cancer models.

Cancer biology & therapy

Sun JD, Liu Q, Ahluwalia D, Ferraro DJ, Wang Y, Jung D, Matteucci MD, Hart CP

Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models.

Clinical cancer research : an official journal of the American Association for Cancer Research

Benito J, Ramirez MS, Millward NZ, Velez J, Harutyunyan KG, Lu H, Shi YX, Matre P, Jacamo R, Ma H, Konoplev S, McQueen T, Volgin A, Protopopova M, Mu H, Lee J, Bhattacharya PK, Marszalek JR, Davis RE, Bankson JA, Cortes JE, Hart CP, Andreeff M, Konopleva M

Combination treatment with hypoxia-activated prodrug evofosfamide (TH-302) and mTOR inhibitors results in enhanced antitumor efficacy in preclinical renal cell carcinoma models.

American journal of cancer research

Sun JD, Ahluwalia D, Liu Q, Li W, Wang Y, Meng F, Bhupathi D, Matteucci MD, Hart CP

Enhancement of hypoxia-activated prodrug TH-302 anti-tumor activity by Chk1 inhibition.

BMC cancer

Meng F, Bhupathi D, Sun JD, Liu Q, Ahluwalia D, Wang Y, Matteucci MD, Hart CP

TH-302 in Combination with Radiotherapy Enhances the Therapeutic Outcome and Is Associated with Pretreatment [18F]HX4 Hypoxia PET Imaging.

Clinical cancer research : an official journal of the American Association for Cancer Research

Peeters SG, Zegers CM, Biemans R, Lieuwes NG, van Stiphout RG, Yaromina A, Sun JD, Hart CP, Windhorst AD, van Elmpt W, Dubois LJ, Lambin P

Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302.

Cancer & metabolism

Wojtkowiak JW, Cornnell HC, Matsumoto S, Saito K, Takakusagi Y, Dutta P, Kim M, Zhang X, Leos R, Bailey KM, Martinez G, Lloyd MC, Weber C, Mitchell JB, Lynch RM, Baker AF, Gatenby RA, Rejniak KA, Hart C, Krishna MC, Gillies RJ

Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer.

Cancer biology & therapy

Sun JD, Liu Q, Ahluwalia D, Li W, Meng F, Wang Y, Bhupathi D, Ruprell AS, Hart CP

Evaluation of the "steal" phenomenon on the efficacy of hypoxia activated prodrug TH-302 in pancreatic cancer.

PloS one

Bailey KM, Cornnell HH, Ibrahim-Hashim A, Wojtkowiak JW, Hart CP, Zhang X, Leos R, Martinez GV, Baker AF, Gillies RJ

Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

PloS one

Takakusagi Y, Matsumoto S, Saito K, Matsuo M, Kishimoto S, Wojtkowiak JW, DeGraff W, Kesarwala AH, Choudhuri R, Devasahayam N, Subramanian S, Munasinghe JP, Gillies RJ, Mitchell JB, Hart CP, Krishna MC

Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

Clinical cancer research : an official journal of the American Association for Cancer Research

Portwood S, Lal D, Hsu YC, Vargas R, Johnson MK, Wetzler M, Hart CP, Wang ES

Synergistic induction of apoptosis in multiple myeloma cells by bortezomib and hypoxia-activated prodrug TH-302, in vivo and in vitro.

Molecular cancer therapeutics

Hu J, Van Valckenborgh E, Xu D, Menu E, De Raeve H, De Bruyne E, De Bryune E, Xu S, Van Camp B, Handisides D, Hart CP, Vanderkerken K

Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features.

Blood

Azab AK, Hu J, Quang P, Azab F, Pitsillides C, Awwad R, Thompson B, Maiso P, Sun JD, Hart CP, Roccaro AM, Sacco A, Ngo HT, Lin CP, Kung AL, Carrasco RD, Vanderkerken K, Ghobrial IM

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

Cancer chemotherapy and pharmacology

Liu Q, Sun JD, Wang J, Ahluwalia D, Baker AF, Cranmer LD, Ferraro D, Wang Y, Duan JX, Ammons WS, Curd JG, Matteucci MD, Hart CP

Selective tumor hypoxia targeting by hypoxia-activated prodrug TH-302 inhibits tumor growth in preclinical models of cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

Sun JD, Liu Q, Wang J, Ahluwalia D, Ferraro D, Wang Y, Duan JX, Ammons WS, Curd JG, Matteucci MD, Hart CP

Molecular and cellular pharmacology of the hypoxia-activated prodrug TH-302.

Molecular cancer therapeutics

Meng F, Evans JW, Bhupathi D, Banica M, Lan L, Lorente G, Duan JX, Cai X, Mowday AM, Guise CP, Maroz A, Anderson RF, Patterson AV, Stachelek GC, Glazer PM, Matteucci MD, Hart CP

14-Aminocamptothecins: their synthesis, preclinical activity, and potential use for cancer treatment.

Journal of medicinal chemistry

Duan JX, Cai X, Meng F, Sun JD, Liu Q, Jung D, Jiao H, Matteucci J, Jung B, Bhupathi D, Ahluwalia D, Huang H, Hart CP, Matteucci M

Targeting the multiple myeloma hypoxic niche with TH-302, a hypoxia-activated prodrug.

Blood

Hu J, Handisides DR, Van Valckenborgh E, De Raeve H, Menu E, Vande Broek I, Liu Q, Sun JD, Van Camp B, Hart CP, Vanderkerken K

Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs.

Journal of medicinal chemistry

Duan JX, Jiao H, Kaizerman J, Stanton T, Evans JW, Lan L, Lorente G, Banica M, Jung D, Wang J, Ma H, Li X, Yang Z, Hoffman RM, Ammons WS, Hart CP, Matteucci M