Michael Houghton

Key Research Areas
Associated Researchers
Associated Organizations

Recent Research Projects

The National CIHR Hepatitis C Network (NCHCN)

2015/16-2019/20 • $4,520,000 • PI,CO,Other
Hepatitis C virus (HCV) infection is a global health problem. In Canada, it is estimated that 242,500 individuals are infected with the incidence of approximately 4,000 new cases per year. The majority of newly infected individuals develop persistent infection and chronic liver disease over many...

Atomistic Computational Models To Evaluate Protein-Ligand Off-Target Interactions

2015/16-2019/20 • $150,000 • PI,CO
To be biologically active, small molecules, proteins and other cellular components must physically fit into their binding site(s) within their targets. A century ago, Fischer described this event as a lock-and-key fit. However, in reaching its precise binding location, a ligand (a molecule that...

Canada Excellence Research Chair in Virology

2010/11-2017/18 • $10,000,000 • PI
Hepatitis C virus (HCV) and hepatitis B virus (HBV) remain significant health problems in Canada and worldwide. There are an estimated 200-300 thousand HCV carriers in Canada and 130-170 million worldwide. There are also an estimated with 220-300 thousand HBV carriers in Canada and 350-400...

Mechanism of B cell lymphoproliferative disease associated with hepatitis C infection

2012/13-2016/17 • $175,000 • Scholarship/Fellowship,Other
Approximately 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), with thousands dying yearly from this disease. A subset of HCV patients develop serious complications ranging from skin rashes to joint pain to even kidney failure due to a specific autoimmune...

Infection with HBRV activates TLRs that inhibits PI3K. Inhibition of GSK3 and activation of CREB proteins can reverse this effect with subsequent improvements of patients with PBC.

2015/16-2016/17 • $63,875 • Scholarship/Fellowship,Other
Hepatitis C virus (HCV) treatment has progressed in the past few years with better response rates. Although there has been considerable work in the field, there are still many unanswered questions and many untreated patients. Besides the detrimental liver cirrhosis and hepatocellular carcinoma...

Role of extracellular matrix and inflammatory remodeling in alcohol-induced liver and lung damage

2014/15-2015/16 • $107,750 • Scholarship/Fellowship,Other
At present, it is estimated that there are 300,000 carriers of hepatitis C virus (HCV) in Canada, while worldwide there are around 170 million carriers who are at risk of developing serious liver diseases if left untreated. Despite years of research and development, we only have 2 drugs...

Isolation of a novel human retrovirus associated with primary biliary cirrhosis and fulfillment of koch's postulates in vitro

2011/12-2014/15 • $426,221 • PI,CO
Patients with primary biliary cirrhosis (PBC) develop progressive liver disease and often require liver transplantation. The cause of disease is unknown. It is thought to occur as a result of an infection in subjects that are more susceptible to disease than others. We found evidence of virus...

Evaluation of the diagnostic value of chemokine and cytokine biomarkers and their role in the pathogenesis of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC)

2013/14-2014/15 • $45,000 • Scholarship/Fellowship,Other
Primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), and autoimmune hepatitis (AIH) are three common chronic inflammatory liver diseases (combined prevalence of ~1/1000) that account for a significant number of liver transplantations in North America (PSC is within the top five...

Third Canadian Symposium on Hepatitis C Virus

2013/14 • $25,000 • PI,CO
Hepatitis C virus (HCV) affects at least 240,000 people in Canada and causes more years of life lost than any infectious disease in the country. The CIHR and the Public Health Agency of Canada (PHAC) have identified liver disease due to HCV as a major public health problem. Understanding how to...

Screening for Novel NS5B-Inhibitors: Toward Selective and Potent Hepatitis C Virus (HCV) Therapy.

2013/14 • $17,500 • Scholarship/Fellowship,Other
Over 170 million people are living with persistent hepatitis C (HCV) infection in the world, with about 300,000 infected people in Canada alone. No vaccine or potent, well-tolerated drugs are available despite 23 years of research since the discovery of the virus and there is still no licensed...

Patents

METHODS AND COMPOSITIONS FOR DIAGNOSIS OF INFLAMMATORY LIVER DISEASE

The present disclosure provides methods and compositions that find use in facilitating a diagnosis of inflammatory liver disease in a subject. The methods and compositions generally involve detection of eotaxin-3 (E3) levels, either alone or with levels of eotaxin-1 (E1), and optionally, with levels of CCL22 and, further optionally, with levels of IL15. These levels can be used to facilitate a diagnosis of a liver disease of at least one of autoimmune hepatitis (AIH), primary biliary...
Related applications: CA20132883711, WO2013IB02611, EP20130835859

HEPATITIS C VIRUS IMMUNOGENIC COMPOSITIONS AND METHODS OF USE THEREOF

The present disclosure provides immunogenic compositions comprising HCV El and E2 polypeptides. The immunogenic compositions are useful in carrying out methods of inducing an immune response to HCV. The present disclosure further provides methods of stimulating an immune response to HCV in an individual.
Related applications: WO2013IB03029

IMMUNOMODULATORY PEPTIDES AND METHODS OF USE THEREOF

The present disclosure provides peptides that modulate an immune response in an individual. The present disclosure provides peptides that modulate cellular responses in vitro. The present disclosure provides compositions comprising the peptides. The peptides and compositions are useful in methods of modulating an immune response in an individual, which methods are also provided.
Related applications: CA20132891974, EP20130856783, EP20130856783, WO2013IB60289

SYSTEMS AND METHODS OF SELECTING COMPOUNDS WITH REDUCED RISK OF CARDIOTOXICITY

Provided herein are systems and methods for selecting compounds that have reduced risk of cardiotoxicity or which are not likely to be cardiotoxic. As an example, a system and method can include a computational dynamic model combined with a high throughput screening in silico that mimics one of the most important ion channels associated with cardiotoxicity, namely the human Ether-a-go-go Related Gene (hERG) channel. Also provided herein are systems and methods for redesigning compounds that...
Related applications: WO2014CA51205, EP20140868747, EP20140868747, CA20142933446

E1E2 HCV VACCINES AND METHODS OF USE

The present disclosure provides immunogenic compositions comprising HCV El, E2, or E1/E2 polypeptides from two or more different HCV genotypes. The present disclosure provides immunogenic compositions comprising HCV E2 or E1/E2 polypeptides from two or more different HCV genotypes. The immunogenic compositions are useful in carrying out methods of inducing an immune response to HCV. The present disclosure further provides methods of stimulating an immune response to HCV in an individual.
Related applications: EP20190215826, CA20142909586, EP20140884476, EP20140884476, WO2014IB01972

METHODS AND COMPOSITIONS IN DIAGNOSIS OF CHRONIC FATIGUE SYNDROME/MYALGIC ENCEPHALOMYELITIS

The present disclosure provides methods and compositions that find use in facilitating a diagnosis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in a subject. The methods and compositions involve measurement of at least one of proteins: IL-16, IL-7, VEGF, CXCL9, CX3CL1, CCL24, CCL19, and CCL11 in a body fluid sample of a subject suspected of having CFS/ME. Levels of one or more of the aforementioned proteins can be used to facilitate a diagnosis of a CFS/ME and/or confirm a...
Related applications: WO2016CA00022

HEPATITIS C VIRUS IMMUNOGENIC COMPOSITIONS AND METHODS OF USE THEREOF

The present disclosure provides heterodimeric polypeptides comprising: 1) a variant hepatitis C virus (HCV) E2 polypeptide and an HCV El polypeptide; 2) a variant HCV El polypeptide and an HCV E2 polypeptide; or 3) a variant HCV El polypeptide and a variant HCV E2 polypeptide, where the variant HCV E2 polypeptide and/or the HCV El polypeptide comprises one or more T cell epitopes, present in an HCV polypeptide other than an HCV El polypeptide or an HCV E2 polypeptide. The present disclosure...
Related applications: CA20162986342, WO2016IB01051, EP20160820906

HEPATITIS C VIRUS E1/E2 HETERODIMERS AND METHODS OF PRODUCING SAME

The present disclosure provides affinity tagged heterodimeric polypeptides comprising a hepatitis C virus (HCV) El polypeptide and an HCV E2 polypeptide, where one or both of the El and E2 polypeptides comprises an affinity tag. The present disclosure provides a method of producing an affinity tagged E1/E2 heterodimer of the present disclosure. The present disclosure provides methods of producing untagged HCV E1/E2 heterodimers. The present disclosure provides HCV E1/E2 heterodimers,...
Related applications: EP20160853179, CA20163000313, WO2016IB56000

SYSTEMS AND METHODS OF SELECTING COMPOUNDS WITH REDUCED RISK OF CARDIOTOXICITY USING CARDIAC SODIUM ION CHANNEL MODELS

Provided herein are systems and methods for selecting compounds that have reduced risk of cardiotoxicity or which are not likely to be cardiotoxic. As an example, a system and method can include a computational dynamic model combined with a high throughput screening in silico that mimics an important ion channels associated with cardiotoxicity, namely the human human cardiac sodium ion (hNa v1.5) channel). In certain embodiments, steered molecular dynamics simulations are used to identify...
Related applications: CA20172975645

RECOMBINANT CARDIOMYOCYTES AND CARDIOMYOCYTE CELL LINES EXPRESSING HERG

The present disclosure relates generally to recombinant cardiomyocytes and cardiomyocyte cell lines overexpressing hERG and uses thereof.
Related applications: CA20173036726, EP20170849960, WO2017CA51076

HEPATITIS C VIRUS IMMUNOGENIC COMPOSITIONS AND METHODS OF USE THEREOF

The present disclosure provides an immunogenic composition comprising: a) a hepatitis C virus (HCV) heterodimeric polypeptide that includes HCV E1 and E2 polypeptides; b) a T-cell epitope polypeptide comprising a T-cell epitope present in an HCV protein other than E1 and E2; and c) a pharmaceutically acceptable excipient. The present disclosure provides a method of inducing an immune response, in an individual, to an HCV polypeptide. The present disclosure provides an immunogenic composition...
Related applications: WO2017IB55714, CA20173037813, EP20170852509

HEPATITIS C VIRUS IMMUNOGENIC COMPOSITIONS AND METHODS OF USE THEREOF

The present disclosure provides immunogenic compositions comprising: a) hepatitis C virus (HCV) E1E2 heterodimers, HCV E2, or HCV E1; and b) an adjuvant, where the adjuvant is a cyclic dinucleotide or an archaeosome. The present disclosure provides methods of inducing an immune response in an individual to HCV, the methods comprising administering to an individual an effective amount of an immunogenic composition of the present disclosure.
Related applications: CA20173038810, EP20170860634, WO2017CA51192

HEPATITIS C VIRUS PEPTIDE COMPOSITIONS AND METHODS OF USE THEREOF

The present disclosure provides an immunogenic composition comprising: a) i) a hepatitis C virus (HCV) heterodimeric polypeptide that includes HCV E1 and E2 polypeptides; ii) an HCV E1 polypeptide; or iii) an HCV E2 polypeptide; b) a polypeptide (also referred to herein as a "T-cell epitope polypeptide" or an "HCV T-cell epitope polypeptide") comprising T-cell epitopes (e.g., CD4+ and CD8+ T-cell epitopes that are conserved among some HCV genotypes and that are presented through one or...
Related applications: WO2019CA50320, EP20190768649

TREATMENT OF AUTOIMMUNE LIVER DISEASE

The present disclosure provides methods and compositions that find use in identifying presence of an advanced stage autoimmune liver disease (ALD) is a subject diagnosed as having ALD. Also provided here are methods and compositions that find use in monitoring effectiveness of treatment of an ALD patient receiving a treatment for the ALD. Also provided here are methods and compositions that find use in identifying subjects suffering from a relapse of ALD. The methods and compositions of the...
Related applications: WO2019US27975

NON-PEPTIDIC HETEROCYCLE-CONTAINING COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

The present disclosure provides non-peptidic heterocycle-containing amylin receptor antagonist compounds, compositions that include the subject compounds, methods for preparing and using the amylin receptor antagonists, and compositions containing the amylin receptor antagonists for treating, preventing, or ameliorating Alzheimer's disease. Aspects of the present disclosure include a method of inhibiting activity of an amylin receptor by administering to a subject in need thereof a...
Related applications: WO2020CA50537