Associate and Adjunct members

Brouhard, Gary, Associate Member
gary.brouhard [at] mcgill.ca
Cells of the human body adopt a range of shapes, from the pancake-flat skin cells of the inner cheek to the tree-like neurons of the hippocampus. How does a cell become a tree and not a pancake? The shape of a cell is determined by an underlying cellular skeleton, or cytoskeleton, just as the shape of a vertebrate’s body is determined by its bones. The Brouhard lab studies the “bones” of the cytoskeleton, polymers known as microtubules — how they are formed and how their formation changes a cell’s behavior. Cells can build an amazing variety of structures from microtubules, structures notable for their range of shapes, their ability to respond to stimulus, and their motility. Our scientific interests are in the biophysical mechanisms by which cells engineer these large-scale structures—in other words, the physical basis of cell shape and organization. Microtubules are prominent drug targets in cancer therapy and their misregulation underlies many brain diseases. The Brouhard lab uses biophysics, cell biology, and biochemistry to perform basic health science research that is oriented toward understanding and treating these diseases.

Drouin, Jacques, Adjunct Member
drouinj [at] ircm.qc.ca
We study transcriptional mechanisms controlling cell differentiation, cell identity and hormone action. These studies use the pituitary gland as a convenient model since it is a relatively simple tissue composed of six related cell types. A particular emphasis is placed on novel transcription factors cloned in the lab, such as the homeobox transcription factors Pitx1/2/3 and Tbox factor Tpit.
The role of Pitx1, Tbx4 and Tbx5 in specification of limb identity is also investigated with a particular emphasis on the evolutionary more recent program from hindlimb development.
Classical molecular biology approaches, incl. mouse models, are combined with recent genome-wide technologies, such as microarray-based profiling and ChipSeq, for a global view of regulatory mechanisms.

Fabian, Marc, Associate Member
marc.fabian [at] mcgill.ca
Post-transcriptional control (PTC) programs regulate protein production after a messenger (m) RNA is transcribed from its DNA template. Many PTC programs control protein production by repressing mRNA translation and/or initiating mRNA destabilization, events collectively referred to as ‘silencing’. These programs are in general mediated by RNA binding proteins and ribonucleoprotein complexes that are recruited to specific mRNAs in order to engender silencing. Given their pervasive use, it is not surprising that many human cancers, as well as many other disorders, are associated with defects in gene silencing networks. The overall theme of my research program is to investigate how microRNAs, RNA binding proteins and ribonucleoprotein complexes translationally repress and/or destabilize target mRNAs in mammalian cells. Ultimately, we wish to use this knowledge to develop new biotechnologies and to identify how aberrant post-transcriptional regulation of gene expression is linked to human disease.

Kiss, Robert Scott, Associate Member
Robert.kiss [at] mcgill.ca
My research focuses on the intracellular trafficking of cholesterol, especially how it relates to disease processes such as obesity, diabetes, lipid storage disease and atherosclerosis. Specifically, I study lipoprotein receptor/ligand endocytosis; intracellular trafficking of proteins and lipids including cholesterol and glycosphingolipids; signaling and regulation of lipid efflux; genetics of human dyslipidemias; the relationship between the immune system and atherosclerosis; intracellular trafficking of cholesterol and glycosphingolipids, as it pertains to lipid storage diseases, atherosclerosis and lipoprotein metabolism.

Lukacs, Gergely, Associate Member
gergely.lukacs [at] mcgill.ca
The cystic fibrosis gene product, CFTR, is a multidomain, polytopic plasma membrane protein that belongs to the ATP-Binding Cassette transporter family. The chloride channel activity of CFTR is indispensable for normal transcellular salt and water transport in numerous organs (e.g. gastrointestinal tract, pancreas and sweat duct) and for the homeostasis of airway surface liquid layer. Our long-term goal is to elucidate the molecular and cellular basis of cystic fibrosis, one of the most prevalent genetic diseases in the Caucasian population, caused by mutations interfering with the folding, stability, activity and/or membrane trafficking of the channel. To achieve this goal, we utilize a combination of biochemical, biophysical, cell biological and genetic techniques. Another aspect of our inquiries is to gain insights into the recognition and elimination mechanism of non-native membrane proteins from post-ER/Golgi compartments in mammalian cells. The peripheral quality control of integral membrane proteins likely represents a fundamental protective mechanism against the accumulation of aggregation prone and toxic polypeptides that are generated by cellular stresses or mutations. Using conditionally misfolded model proteins, we aim at identifying the machinery responsible for the disposal of non-native plasma membrane proteins. The structural and biochemical basis of ubiquitin recognition as an endocytic and postendocytic sorting signal is also investigated.

McCaffrey, Luke, Associate Member
luke.mccaffrey [at] mcgill.ca
My lab is interested in the mechanisms governing the transition of normal cells to cancer cells, with a focus on breast cancer. We study tissue homeostasis to characterize elements that maintain normal tissue architecture and their function in a tumor suppressive role, and how these elements are altered to enable cancer initiation and progression. We use a range of experimental systems including patient derived xenografts, organoids, transgenic animal models coupled with multiplexed imaging and live-video microscopy to gain insights into the dynamic nature of cancer initiation and progression. Our long-term objectives are to better predict patients that will develop breast cancer and identify therapeutic targets to prevent cancer development.

Ortega, Joaquin, Associate Member
joaquin.ortega [at] mcgill.ca
Understanding how Ribosomes Assemble - Ribosomes are responsible for the process of decoding mRNA into proteins, a process essential to sustain life. Bacteria with defects in ribosome biogenesis exhibit slower growth and severely reduced ability to cause disease. Ribosomes are arguably the most complex molecular nanomachines in the cell. They are comprised of a small (30S) and a large (50S) subunit and overall they contain over 50 different components. In recent years, extraordinary efforts in structural biology have provided atomic structures of the ribosome generating a detailed three-dimensional view of the process of protein synthesis and how antibiotics currently used in the clinic function by targeting the mature ribosome. These structures have been essential to both find new antibiotics as well as to make existing ones more powerful. However, atomic resolution structures of ribosome assembly intermediates have not been obtained and the present structural understanding of the intricate process of assembly of the ribosome is very superficial. This void of knowledge limits our ability to develop new antibiotics targeting the process of ribosome assembly. Our laboratory uses cryo-EM to obtain atomic resolution structures of ribosome assembly intermediates and visualize in 3D the complexity of this process. Structural biology techniques have been instrumental in the discovery of antibiotics targeting the mature ribosome. The atomic resolution structures of immature ribosomes obtained in our laboratory are having the same impact and are providing an extensive reservoir for the discovery of new antibiotics that target ribosome assembly.

Purisima, Enrico, Adjunct Member
rico [at] bri.nrc.ca
We are interested in developing and applying computational tools for elucidating the structural and energetic determinants of molecular recognition. Of particular interest is the role of solvation in binding interactions and conformational stability. Areas of active research include continuum solvation models, conformational search methods, binding free energy calculations and computer-aided molecular design of small molecules and proteins. In parallel, we also have a bioinformatics stream. Areas of interest include analysis of signaling networks, identification of cancer biomarkers, comparative genomics of yeast and related fungi and data mining of genomes for the discovery of novel transcription factors or rewiring of the functions of known ones.

Rak, Janusz, Associate Member
janusz.rak [at] mcgill.ca
Studies on how oncogenic pathways influence intercellular communication in pediatric and adult cancers, especially during the course of tumour angiogenesis. This includes the biology of microvesicles (oncosomes) and signaling through the effectors of the coagulation system (tissue factor pathway), and how these events affect interactions between tumour initiating (stem), or metastatic cells and the vasculature. Exploration of therapeutic consequences of these effects.

Richard, Stéphane, Associate Member
stephane.richard [at] mcgill.ca
Stéphane Richard is a scientific expert in molecular biology research in the fields of cancer and neuroscience. His research is aimed at understanding the roles of protein arginine methylation and RNA binding proteins in diseases such as cancer and multiple sclerosis. Dr. Richard's group is actively pursing the molecular roles of protein methylation and RNA binding proteins in epigenetics, RNA metabolism, and DNA damage signaling.

St-Pierre, Julie, Adjunct Member
julie.st-pierre [at] uottawa.ca
Mitochondria play a central role in basic physiological functions by producing most of the cellular ATP. Furthermore, mitochondria are important for cellular functions such as heat production, generation of reactive oxygen species (ros) and execution of the apoptotic program. Given the key role of mitochondria in various cellular events, it is not surprising that mitochondrial dysfunctions are seen in many pathological conditions such as neurodegeneration, diabetes, aging and cancer. The aim of my research is to understand the regulation of mitochondrial metabolism under physiological and pathological conditions using unbiased screening approaches, notably metabolic profiling in combination with global gene expression analysis.

Salavati, Reza, Associate Member
reza.salavati [at] mcgill.ca
The three related species of trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, cause serious human and animal diseases, with a very high incidence and mortality rate if untreated. There are no vaccines for these pathogens, the drugs are toxic with limited effectiveness, and drug resistance is emerging. The availability of the genome sequences of these organisms since 2005 has dramatically expanded our knowledge of their biology; however, a major obstacle has since been acknowledged: the majority of trypanosomatid genes are not found in any other organism, making it almost impossible to use homology-based methods for inferring their functions from their sequences. Our lab is focused on development of novel computational and experimental methods for functional and structural characterization of trypanosomatid genomes. We are also involved in development of high-throughput methods for identification of novel chemical inhibitors of essential trypanosomatid proteins, particularly the editing complex of T. brucei. Functional characterization of some of the key trypanosomatid proteins that are involved in RNA editing is also among the major research topics of our lab.

Schurr, Erwin, Associate Member
erwin [at] igloo.epi.mcgill.ca
Our research is aimed at the identification of genes contributing to host resistance and susceptibility to tuberculosis and leprosy, two major human infectious diseases.

Siegel, Peter, Associate Member
peter.siegel [at] mcgill.ca
My lab is interested in understanding processes that control the ability of breast cancer cells to spread or "metastasize" to bone and soft tissues. We employ in vivo models for the selection of highly metastatic tumor cell populations which are then subjected to gene expression profiling to identify genes that are associated with the metastatic phenotype. In addition, we focus on cooperation between the ErbB-2 and TGF-β signaling pathways in promoting breast cancer metastasis in animal models.

Topisirovic, Ivan, Associate Member
ivan.topisirovic [at] mcgill.ca
Our lab focuses on studying the mechanisms of post-transcriptional regulation of gene expression including those occurring at the level of translation and folding and/or degradation of newly synthesized polypeptides. Specifically, we are interested in understanding how signaling pathways such as mTOR affect post-transcriptional gene expression networks during stress response and how these changes impact on cellular proliferation, growth and energetics in normal vs. malignantly transformed cells.

Tsantrizos, Youla, Associate Member
youla.tsantrizos [at] mcgill.ca
Research in my laboratory involves elucidating the cellular and molecular Our projects focus on the design and synthesis of small molecule ligands that can bind to mammalian or microbial targets modulating their function. Our main objective is to design chemical tools that can facilitate investigations into the biological role of proteins associated with a disease state.
Currently, a number of our projects involve structure-based ligand design targeting the human enzyme farnesyl pyrophosphate synthase (hFPPS). A key objective of these projects is to synthesize novel active site or allosteric site inhibitors of hFPPS that could potentially serve as “leads” for the design of better therapeutic agents for the treatment of osteoporosis, cancer and viral infections. However, the ultimate goal of these studies is to provide greater insight into the biological significance of post-translational prenylation of proteins and elucidate the role of hFPPS in the innate immune response during viral infections.

Turcotte, Bernard, Associate Member
bernard.turcotte [at] mcgill.ca
Research in my laboratory relates to functional genomics in budding yeast and pathogenic fungi. We are focusing on the Gal4 family of transcriptional regulators that includes over fifty members in budding yeast. The function of many of these Gal4 members is unknown or poorly defined. To better understand the role of these transcriptional regulators and identify their target genes, we are using various approaches including genome-wide location analysis and expression profiling as well as genetics. We are also determining the role of related Gal4 members in conferring resistance to antifungal drugs in the human pathogens Candida albicans and C. glabrata. Another project is aimed at identifying new compounds with antifungal activity. Finally, my lab is also interested in developing compounds with antibacterial activity.

Ursini-Siegel, Josie, Associate Member
giuseppina.ursini-siegel [at] mcgill.ca
(1) Defining the mechanism by which ShcA signaling in breast cancer cells controls both tumor neovascularization and blood vessel integrity. (2) Defining the mechanism by which ShcA signaling in breast cancer cells establishes a local immunosuppressive state to favour cancer progression. (3) Translate the SRIS into a clinically-relevant diagnostic tool to predict the outcome of HER2 and basal breast cancer patients. This has enormous clinical potential since there is currently no screening test to stratify these patients within these subtypes based on outcome. (4) Identify the contribution of the individual ShcA isoforms during breast cancer progression.

Wing, Simon, Associate Member
simon.wing [at] mcgill.ca
We explore the function and regulation of the ubiquitin dependent proteolytic pathway in mammalian systems with particular attention to its role in the activated protein degradation occurring in atrophying skeletal muscle, its role in the developmental process of sperm cell maturation and in the control of circadian rhythms.

Yang, Xiang-Jiao, Associate Member
xiang-jiao.yang [at] mcgill.ca
We have been interested in the question of how physiological and environmental signals get into individual cells of multicullar organisms and regulate chromatin structure and gene expression in normal and diseased states. In particular, we have been deciphering the function and regulation of histone-modifying enzymes, esp. histone acetyltransferases and deacetylases. One emerging project in the laboratory is how these enzymes and their regulators play a role in self-renewal and differentiation of various types of stem cells, including ES (embryonic stem) and iPS (induced pluripotent stem) cells.

Zeytuni, Natalie, Associate Member
natalie.zeytuni [at] mcgill.ca
Dr. Zeytuni’s lab studies bacterial secretions systems and membrane transportation. Bacterial secretion systems are essential membrane embedded protein machineries, enabling bacteria to obtain nutrients, communicate, protect against biological and chemical agents, as well as facilitate disease through the delivery of virulence factors. Dr. Zeytuni’s lab integrates structural biology techniques including cryo-EM and X-ray crystallography with biochemical, biophysical and genetic approaches to determine the structure and decipher the molecular mechanisms of these transport machineries.