Michael Weinfeld

Key Research Areas
Associated Researchers
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Recent Research Projects

Polynucleotide kinase: its role in DNA strand break repair and a potential therapeutic target to enhance radio- and chemotherapy

2014/15-2018/19 • $952,465 • PI
A problem frequently encountered in cancer therapy is that of tumour cell resistance to therapeutic agents, so that although the majority of cells in a tumour will be destroyed, a small fraction will survive, and have the potential to metastasize. At present our ability to predict tumour...

Nanodelivery systems for targeted inhibition of DNA repair in the treatment of unresectable lung cancer

2018/19 • $73,768 • PI,CO
Lung cancer is the second most common cancer in both men and women and the number one cause of cancer related death in North America. Lung cancer is rarely detected at the early stages of disease because symptoms tend to be mild and non-specific. When diagnosed, 60-75% of patients have advanced...

Nano-delivery of novel inhibitors of polynucleotide kinase/phosphatase (PNKP) for tumor targeted sensitization of colorectal cancer to DNA damage.

2018/19 • $35,000 • Scholarship/Fellowship,Other
Colorectal cancer (CC) is the 4th most common cause of cancer-associated death worldwide. Surgery, chemotherapy (CT), and radiotherapy (RT) are the most common treatments for CC. However, these treatments are rarely curative and cause severe side effects in patients. Moreover, 50% reoccurrence...

Regulation of PNKP and XRCC4 in non-homologous end-joining by dynamic, reversible protein phosphorylation.

2012/13-2017/18 • $1,076,131 • PI,CO
Ionizing radiation (IR) is used extensively in the treatment of many forms of cancer. It acts by inducing lethal DNA damage, in particular a form called a DNA double strand break or DSB. The major pathway for the repair of IR-induced DSBs in human cells is called non-homologous end-joining or...

Mechanisms of arsenic carcinogenesis

2014/15-2017/18 • $702,720 • PI,CO
Project summary: Arsenic is now recognized as one of the most important environmental agents causing cancers of the skin, bladder, and lungs. However, it is uncertain what level of arsenic is acceptable because scientists don't know how arsenic causes these cancers. The primary objective of this...

Structure/Function of the DNA Repair Enzyme, Polynucleotide Kinase/Phosphatase

2011/12-2016/17 • $844,851 • PI,CO
All cancers initiate through genetic mutations that arise as a result of damage to DNA. Our cells contain elaborate mechanisms that have evolved to recognize and repair damaged DNA, thereby protecting our genetic information. Our lab studies the proteins that are involved in detecting DNA damage...

Targeting DNA repair in cancer therapy: the promising role of synthetic lethality

2013/14-2016/17 • $135,000 • Scholarship/Fellowship,Other
This research projects deals with cancer therapy and how to introduce a new targeted therapy for some types of cancer by making use of their biological characteristics. It is known that tumors often fail to make particular proteins. This is not fatal for the tumor cells and in fact is sometimes...

Preclinical evaluation of polynucleotide kinase/phosphatase as a therapeutic target.

2011/12-2014/15 • $357,058 • PI,CO
Despite major advances in targeted chemotherapy, the major forms of therapy continue to be surgery, radiotherapy and conventional chemotherapy. The main target for radiotherapy, and many conventional drugs, is the cell's DNA. Not surprisingly, the levels of DNA damage and the repair of that...

Chemical genetic screen for cell surface receptors that control cancer stem cell differentiation

2014/15 • $100,000 • PI,CO
We aim to identify materials that favor or suppress growth of cancer stem cells (CSC). These cells are hypothesized to be at the origin of many cancers. They are resistant to drugs and radiation treatment and a few CSCs surviving the treatment could re-initiate the growth of the tumor. Recent...

Polynucleotide kinase: its role in DNA single-strand break repair and a potential therapeutic target to enhance radio- and chemotherapy.

2010/11-2013/14 • $531,872 • PI,CO
A problem frequently encountered in cancer therapy is that of tumour cell resistance to therapeutic agents, so that although the majority of cells in a tumour will be destroyed, a small fraction will survive, and have the potential to metastasize. At present our ability to predict tumour...

Functional roles of keratinocyte derived anti-fibrogenic factors in wound healing

2010/11-2012/13 • $257,976 • PI,CO
Non-healing and over-healing wounds are considered serious pathologic disorders with far reaching clinical and economic implications. Like any other dynamic biological process, there must be a set of factors that gradually slow down and/or terminate the dynamic healing process in the late stages...

Mechanisms of arsenic carcinogenesis

2010/11-2011/12 • $193,307 • PI,CO
Arsenic is now recognized as one of the most important environmental agents causing cancers of the skin, bladder, and lungs. However, it is uncertain what level of arsenic is acceptable because scientists don~t know how arsenic causes these cancers. The primary objective of this study is to gain...

Small molecule inhibitor of polynucleotide kinase/phosphatase and uses thereof in cancer treatment.

2010/11 • $150,000 • PI,CO
Radiotherapy and many chemotherapeutic agents used in the treatment of cancer kill the cancer cells by damaging the DNA within the cells. Resistance to the treatment can arise because cells possess enzymes that can repair DNA damage. There is now increasing interest in discovering small chemical...

Patents

SMALL MOLECULE INHIBITORS OF POLYNUCLEOTIDE KINASE/PHOSPHATASE, POLY(ADP-RIBOSE) POLYMERASE AND USES THEREOF

The present invention generally relates to use of compounds and compositions as a chemosensitizers and/or radiosensitizers and/or inhibitors of PNKP phosphatase activity. The present invention provides pharmaceutical combinations and/or a pharmaceutically acceptable salt thereof, kits containing such compounds and/composition and methods of using such compounds and/or compositions.
Related applications: EP20100782872, WO2010CA00846, CA20102764234, EP20100782872

SYNTHETIC LETHALITY IN CANCER

There is described herein compounds, compositions and methods for inducing synthetic lethality in a cancer cell(s).
Related applications: WO2011CA01229, EP20110837365, CA20112816929

IMIDOPIPERIDINE COMPOUNDS AS INHIBITORS OF HUMAN POLYNUCLEOTIDE KINASE PHOSPHATASE

There is described herein imidopiperidine compounds as inhibitors of human polynucleotide kinase phosphatase.
Related applications: WO2018CA50422

BIOREDUCTIVELY-ACTIVATED COMPOUNDS, THEIR PRODRUGS, RADIOPHARMACEUTICALS, THE COMPOSITIONS, AND THEIR APPLICATIONS IN MULTIMODAL THERANOSTIC MANAGEMENT OF HYPOXIA DISEASES INCLUDING CANCER

Described herein are bioreductively- activated compounds, their prodrugs, radiopharmaceuticals, the compositions, and their application in multimodal theranostic management of hypoxia diseases including cancer.
Related applications: EP20180859438, WO2018CA51166

MARKERS, CONJUGATES, COMPOSITIONS AND METHODS FOR HYPOXIA IMAGING, MAPPING, AND THERAPY

Described herein are markers, conjugates, compositions and methods for hypoxia imaging, mapping, and therapy. A compound comprising bio-reductively activated (BA) arm, linker arm and a mapping click wherein BA contains one for more of substituted or unsubstituted 2/4/5-substituted nitroimidazoles, or substituted benzotriazene-1,4-dioxides, or substituted 1,2,3/1,2,4-triazoles, or substituted 1,4-benzoquinones, or a combination of two homo-or hetero BA moieties, wherein linker arm contains...
Related applications: WO2018CA51165