In The News

Sidhu lab post-doctoral fellow Dr. Wei Zhang wins prestigious Cancer Research Society award


October 2017. Dr. Wei Zhang, a post-doctoral fellow in the Sidhu lab, has been awarded one of the highly prestigious "Scholarships for the Next Generation of Scientists" by the Cancer Research Society. Among the 4 applications funded, Dr. Zhang’s application was ranked first in the competition, which garnered him a special award funded by BMO Bank of Montreal. As part of its 200th anniversary celebrations, BMO Bank of Montreal is partnering with the Cancer Research Society to fund the best applicant in the competition.

The Scholarships for the Next Generation of Scientists is a funding program that aims to support the future generation of Canadian researchers. The two-part award consists of post-doctoral support for end-of-fellowship trainees followed by a new investigator operating grant, thus bridging the transition from trainee to faculty.

Dr. Zhang joined the Sidhu lab in 2012. To support his post-doctoral studies, he obtained a highly competitive CIHR post-doctoral fellowship, as well as a Mitacs Elevate fellowship. Wei has been instrumental in moving the ubiquitin variant (UbV) program forward. Indeed, Wei has published 9 articles from his work in the Sidhu lab, including 4 as first author. One more article is in press. His outstanding achievements were recognized in 2016 with a Mitacs post-doctoral Outstanding Innovation award. The Cancer Research Society award will most certainly contribute to Wei’s continued success as a burgeoning scientist. Congratulations Wei!

Read Wei's interview on the Donnelly Centre News.



Sidhu lab study uncovers non-canonical binding specificities for SH3 domains


September 2017. A study led by Sidhu lab research associate Dr. Joan Teyra, and recently published in the journal Structure, uncovers non-canonical specificity profiles for SH3 domains. In line with previous Sidhu lab studies on peptide recognition modules (PRM) carried out with PDZ and WW domains, the current study presents a comprehensive specificity map for 115 SH3 domains, obtained by a newly developed technology that employs peptide phage display and deep sequencing analysis (in collaboration with Donnelly Centre Computational Biologist Dr. Gary Bader). The data highlight that amino acids in the vicinity of the canonical proline-rich ("PxxP") motif contribute to binding and that many SH3 domains bind to non-canonical motifs. In this regard, the crystal structures of two SH3 domains binding non-canonical peptides reveal novel binding modes. The study contributes to a deeper understanding of SH3 domains, which participate in many eukaryotic signal transduction events that may be deregulated in diseases such as cancer. It also expands the range of partners that can be predicted to bind SH3-containing proteins.

The broad significance of this study was recently highlighted in the Donnelly Centre News.



UPDATED - Dr. Sidhu highlights the high contribution of academic research in drug development

In June 2015, Dr. Sidhu was interviewed for the CBC news item "Spotlight on Alexion's pricing of rare-disease drug Soliris" as an expert in the process of developing antibody-based drugs. Dr. Sidhu highlighted the fact that a large part of the research required to develop a drug is performed in academic labs funded by public money, and that the real cost of drug development should therefore be more transparent. The news item was about the high cost of the antibody drug "Soliris", and how that cost is based on what the market can bear, rather than on the real cost of developing the drug. Watch Dr. Sidhu's appearance on CBC's The National here.

In June 2017, Dr. Sidhu was interviewed by Anna Maria Tremonti on CBC radio's The Current to discuss orphan drugs and drug pricing, in the context of Soliris. The program featured a patient who greatly benefits from taking Soliris, but had to jump through many hurdles to be approved for help in funding this extremely onerous drug ($750,000/y at the required dose). Dr. Sidhu highlighted the fact that we as the public, should be better informed about what justifies such high pricing, when the costs of producing antibody drugs has substantially decreased in the last few years thanks to new technology. He also highlighted the fact that academic institutions, whose research greatly contributes to knowledge used for drug development, have to do a better job of translating that knowledge into health solutions themselves, rather than relying on pharmaceutical companies whose primary goal is to increase profits. Read more about that story here or hear the full interview (Dr. Sidhu's segment starts at 07:15).

In September 2017, Canada's Patented Medicine Prices Review Board announced that Alexion Pharmaceuticals, the maker of Soliris, would have to lower the drug price, as reported by CBC News.



Sidhu lab graduate student Greg Martyn receives Yip Award

August 2017. Graduate student Greg Martyn is one of the recipients of the 2017 Cecil Yip Doctoral Research Award granted by the Donnelly Centre (University of Toronto) to students who conduct innovative and highly collaborative work that crosses formal disciplinary boundaries.
Greg is working on a project aimed at the development of a general method to enhance SH2 domain binding affinity and is co-supervised by Dr. Mike Moran (SickKids Research Institute). The project was started as part of a CIHR-funded collaboration between the Sidhu and Moran groups to predict and profile peptide recognition domains, specifically pertaining to in-depth studies of SH2 domains and the determinants of phosphotyrosine binding. This project yielded a high profile publication in Proteomics to which Greg contributed (Tong, J., Cao, B., Martyn, G. D., Krieger, J. R., Taylor, P., Yates, B., Sidhu, S. S., Li, S. S. C., Mao, X. & Moran, M. F. (2016) "Protein-phosphotyrosine proteome profiling by superbinder-SH2 domain affinity purification mass spectrometry, sSH2- AP-MS". PMID: 27880036).
Greg’s current project will continue this stream of investigations to create phosphotyrosine “superbinders” utilizing our libraries of synthetic peptides as well as the mass spectrometry expertise of the Moran laboratory.

Congratulations Greg!



Protein-engineered ubiquitin variants designed in the Sidhu lab may lead to new treatments for deadly viral infections


May 2017. In a study recently published in PLoS Pathogens, Dr. Sidhu and colleagues describe how they applied ubiquitin variant (Ubv) technology to create anti-viral compounds.

The Ubv technology consists of screening phage-displayed libraries of ubiquitin variants against a ubiquitin-binding target of interest to obtain Ubvs that have high affinity and specificity for the target. By displacing wild type ubiquitin from the target, the Ubv can modulate its function. Given the increasingly recognized role of ubiquitin in affecting biological processes, Dr. Sidhu's group first focused on generating Ubvs for many enzymes of the human Ubiquitin Proteasome System.

In this study, led by senior post-doctoral fellow Dr. Wei Zhang, the group collaborated with viral biology experts Dr. Marjolein Kikkert (Leiden University Medical Center) and Dr. Brian Mark (University of Manitoba) to target viral ubiquitin-binding enzymes. Many viruses encode deubiquitinases (DUBs, enzymes that remove ubiquitin from proteins) that are crucial for viral replication and pathogenicity. Dr. Zhang generated Ubvs that specifically bind DUBs of the MERS virus and inhibit their function. The study demonstrates that the Ubvs can act as potent anti-viral agents. Once coupled to an efficient delivery system, Ubvs could thus become novel effective drugs against many viruses that depend on ubiquitin-binding enzymes.

Read a news feature on this story on the Donnelly Centre website.



Sidhu lab receives new funding from a Terry Fox Research Institute's Program Grant to design novel brain cancer therapies

April 2017. Dr. Sidhu, together with Dr. Jason Moffat (University of Toronto) and Dr. Sheila Singh (McMaster University) were recently awarded a prestigious Terry Fox Research Institute (TFRI) New Frontiers Program Project Grant to develop antibody-based therapies for brain cancer (glioblastoma, or GBM).

The Program includes several Core platforms, one of which is the Toronto Recombinant Antibody Centre (TRAC) that will generate antibody candidates to be tested in GBM models. The project will also benefit from the IgG production capabilities of the Centre for the Commercialization of Antibodies and Biologics (CCAB).

The Core platform was recently featured in a blog post by TFRI. Read it here.

Dr. Sidhu awarded Genome Canada Disruptive Innovations in Genomics Grant

December 2016. Dr. Sidhu, along with colleagues Dr. El Bachir Affar from Université de Montréal and Dr. Roman Melnyk from SickKids Research Institute, have been awarded a Genome Canada Disruptive Innovations in Genomics (DIG) 3-year grant for their project entitled "Synthetic inhibitors of ubiquitin-binding cancer targets". The grant will support the development of ubiquitin variants as inhibitors of cell signaling and potential cancer drugs. The project is jointly supported by Ubiquitech, a recently launched Toronto biotech company that specializes in the validation, production and commercialization of ubiquitin variants as research reagents and biotherapeutics, and by matching institutional and industrial partners. Read Genome Canada's press release here.



Postdoctoral Fellow Dr. Gino Gallo awarded 2016 Charles H. Best Fellowship

August 2016. Dr. Eugenio (Gino) Gallo joined the Sidhu lab in April 2015 after completing a PhD at Carnegie Mellon University. In his current project, Gino is developing synthetic antibodies to integrin receptor proteins as tools to study how integrins contribute to cancer development. The antibodies may also ultimately be candidate biologic drugs to fight cancer. Gino was recently awarded the prestigious 2016 Charles H. Best Postdoctoral Fellowship that each year, supports one outstanding scientist to undertake a project at the Donnelly Centre. Read more about Gino's project here. Congratulations Gino!



The Hon. Elizabeth Dowdeswell, Ontario's Lieutenant Governor, visits the Sidhu lab

May 18, 2016. Dr. Sidhu and members of the Sidhu lab were excited to showcase our research to the Honourable Liz Dowdeswell. Her Honour was at the University of Toronto on her first official visit for an event celebrating youth and innovation. Dr. Sidhu and graduate student, Max London, discussed some of the innovative technology that is used at TRAC and the potential impact on Ontario’s healthcare.




Sidhu lab ubiquitin variant platform yields new and effective modulators of HECT E3 ligases


March 2016. Building on the high throughput synthetic antibody generation pipeline of the TRAC, the Sidhu group is using phage-displayed libraries of small protein variants to generate biologically active modulators of protein function. Libraries of variants based on the ubiquitin scaffold were screened against ubiquitin-binding enzymes, and high affinity ubiquitin variants (Ubvs) were identified (see original study published in Science, led by post-doctoral fellow Andreas Ernst, now a group leader at Goethe-Universität Frankfurt). These Ubvs are capable of modulating the function of their cognate proteins with high potency and specificity.
The new study, published in Molecular Cell and led by CIHR and MITACS Elevate postdoctoral fellow Wei Zhang, together with the collaborating labs of Brenda Schulman, Jason Moffat, Daniela Rotin and Wade Harper, details the characterization of Ubvs targeting HECT E3 ubiquitin ligases that act as both inhibitors and activators of protein function (Zhang et al., "System-wide modulation of HECT E3 ligases with selective ubiquitin variant probes"). Functional and structural studies reveal novel modes of enzyme regulation by Ubvs and biological studies indicate that the Ubvs effectively modulate therapeutically relevant targets. This work demonstrates the versatility of Ubvs for modulating enzyme activity across a family of enzymes, defines mechanisms of action and provides a toolkit for probing enzyme function in an area where modulators were severely lacking until now. It also establishes a general strategy for the highly efficient, systematic development of modulators targeting families of signaling proteins. This strategy is being applied further to other ubiquitin-binding enzymes and also being extended to other small protein scaffolds.




Pharmaceutical giant Celgene injects major funds into academic synthetic antibody research and development

September 2015. The pharmaceutical company Celgene has indicated its intense interest in the development of biologics, notably synthetic antibodies, in the form of a US $25 million sponsorship of the Recombinant Antibody Network (RAN). The RAN, a consortium of US- and Canada-based academic labs dedicated to the development of synthetic antibodies with therapeutic applications, was founded Dr. Sidhu and Drs. Anthony Kossiakoff (UChicago) and Jim Wells (UCSF). The Celgene collaboration will focus on the development of therapeutic antibodies for cancer, inflammation and immunological disorders. "Through this partnership, we are taking a giant step forward in the ultimate goal of the RAN: the systematic targeting of the “extra-cellularome,” the cell-surface proteins that control cancer and other diseases", says Dr. Sidhu. "In the future, we envision that we will be able to precisely target cancer cells at the molecular level, which will provide better therapies for patients". Read the press releases here and here.


University of Toronto's "Medicine by Design" the recipient of a prestigious CFREF grant

In July 2015, the "Medicine by Design" initiative from the University of Toronto received $114 million in funding from the Government of Canada's Canada First Research Excellence Fund (CFREF). This initiative will incorporate new technologies and scientific strategies into the University of Toronto’s regenerative medicine programs, and develop local capacity for manufacturing rapid lab-to-patient technologies that allows Canada to lead the transformation of the global medical industry and become a major international supplier of regenerative medicine technologies. Outstanding scientists at the University of Toronto and affiliated centres and hospitals will participate, including Dr. Sidhu and the Centre for the Commercialization of Antibodies and Biologics (CCAB) he directs. Learn more about Medicine by Design and read the CFREF and University of Toronto press releases.


Drs. Sidhu & Affar receive funding from CQDM/OCE to support ubiquitin variant development

In June 2015, Dr. El Bachir Affar (from the Université de Montréal's Research Centre of the Hôpital Maisonneuve-Rosemont) and Dr. Sidhu secured funding from the CQDM-sponsored "Explore" program, co-sponsored by the Ontario Centres of Excellence. The two-year grant will support the development of variants of ubiquitin (Ubvs) capable of modulating the activity of ubiquitin-binding enzymes. These Ubvs will be invaluable reagents to probe the function of target enzymes and, since many of these enzymes are deregulated in disease, may also serve for the development of therapeutics. Read the CQDM press release here.


Dr. Sidhu wins prestigious Protein Society Award

In February 2015, Dr. Sidhu was awarded the Protein Society's 2015 Christian B. Anfinsen Award that recognizes technological achievement or significant methodological advances in the field of protein science. Read the UofT interview with Dr. Sidhu about the significance of the Award for his research here.




Northern Biologics: Bringing academic discoveries one step closer to patient therapies

In December 2014, a team of scientists from the University of Toronto and University Health Network, including Dr. Sidhu, launched Northern Biologics, an innovative biotechnology company where antibodies first discovered in academic laboratories will be further developed into therapeutic antibodies for the treatment of cancer and fibrosis. The launch received extensive coverage, including in the Globe and Mail (download article) and Yahoo finance. Read the UofT press release here. Most recently, Northern Biologics announced a strategic collaboration with Celgene, a large biotechnology company that manufactures drug therapies for cancer and inflammatory disorders.


Launch of the

The Centre for the Commercialization of Antibodies and Biologics (CCAB), a new Centre of Excellence for Commercialization and Research (CECR) funded by the Government of Canada (see CCAB on NCE website), was launched in December 2014 (view launch event from the Faculty of Medicine). Headed by Dr. Sidhu, the Centre will translate the research discoveries of TRAC and other academic labs into commercial ventures. Read about how the CCAB will tie in with the philosophy of the Donnelly Centre. Download the press release from the Networks of Centres of Excellence.



Visit by the Honourable Ed Holder, Minister of State (Science and Technology) - October 16th 2014

The TRAC team, along with collaborator Dr. Benjamin Neel and members of the Faculty of Medicine Dean's Office were pleased to welcome Minister Holder for a visit to the Donnelly Centre. He was given a tour of the lab and demonstrations of some of the technology and high-throughput equipment used by the TRAC in the production of synthetic antibodies. An update on TRAC success was given by Dr. Pan and Dr. Neel and Pankaj Garg, Megan McLaughlin, Max London and Isabel Leung led demonstrations.


Youth Outreach, St. Basil-the-Great College School visit

On October 7th, 2014, we were pleased to welcome the students of St. Basil's Grade 12 Biotechnology Program to tour the Sidhu lab and the TRAC facilities. Students were given highlights of the research and technology in the lab from Dr. Jarrett Adams, Ms. Megan McLaughlin, and Ms. Isabel Leung.


Protein Engineering Highlights

The Avacata Life Sciences blog recently named two papers from Dr. Sidhu to its top ten list of protein engineering papers that changed the world. The publications by Fellouse et al (2005) and (2006) are cited for having demonstrated that high-affinity binders (10nM range) could be selected from a library where CDRs are composed of only 2 amino acids. See the full top ten list here.

Ebola antibodies

A recent publication in ACS Chemical Biology by Dr. Sidhu and his collaborators at Albert Einstein College of Medicine and the United States Army Medical Research Institute of Infectious Diseases was noted as a potential therapy for future ebola outbreaks. The development of a humanized synthetic antibody to the Sudan ebolavirus (SUDV) was led by Dr. Gang Chen, a member of the TRAC scientific team. Although this is not the strain of ebolavirus currently devastating West African countries, SUDV is extremely lethal. Now that a human version of the antibody previously developed by the team (Koellhoffer et al, 2012) has been developed, a strong potential therapy exists for future outbreaks. Read the press release by the American Chemical Society here.

President of the University of Toronto visit, July 9th 2014

Dr. Meric Gertler, President of the University of Toronto, visited the Sidhu lab on his tour through the Donnelly Centre on July 9th. Dr. Misquitta and members of the Sidhu lab and the TRAC team were delighted to be able to provide a tour of their facilities and share their research with Dr. Gertler and a number of senior administrators.

Kolltan Pharmaceuticals licenses TRAC-developed antibodies, announced December 6th, 2013

Novel anti-KIT receptor antibodies recently developed at TRAC with collaborator Dr. Joseph Schlessinger, were licensed by Kolltan Pharmaceuticals. It is expected that, in addition to possible therapeutic applications, the antibodies will be essential tools for structural biologists. The work in Dr. Sidhu’s lab was led by Dr. Bryce Nelson (read on PNAS.org). See the Koltan press release here.

About Us

Dr. Sachdev Sidhu is an expert in phage display technology and structure-based and combinatorial protein engineering. In 2008, after spending a decade as a principal investigator in the Department of Protein Engineering at Genentech, Inc., Dr. Sidhu joined the University of Toronto to start his academic lab. At Genentech, Dr. Sidhu led the development of phage-displayed synthetic antibody libraries that have since proven to be a rich source of valuable reagents for basic research and potential therapeutics. In addition to antibody engineering, Dr. Sidhu has extensive experience with phage display of other diverse polypeptides, including peptides, peptide-binding domains, hormones and antibody mimics.

The Sidhu lab’s talented scientists, students, technicians and other staff contribute to several projects, and Dr. Sidhu has a successful track record of collaborations with both academic and industry partners, including Drs. Moffat, Kossiakoff, Koide, Wells, Boone, Neel, Rottapel, Shoichet and Reilly (to name a few) and Integrated BioTherapeutics, Genentech, GlaxoSmithKline, Merrimack, SciGenom, and Alnylam Pharmaceuticals (to name a few), respectively. Research in the lab is supported by extensive funding from both public and private sources, including large team grants from Genome Canada and the Ontario Research Fund, to address specific unmet medical needs using protein binders.

The Sidhu lab is located at the Terrence Donnelly Centre for Cellular and Biomolecular Research (The Donnelly Centre). In 2011, Dr. Sidhu expanded his laboratory by launching the Toronto Recombinant Antibody Centre (TRAC), an integrated laboratory with a state-of-the-art, high throughput antibody research platform that has been applied to the generation of therapeutic-grade antibodies against hundreds of antigens. The TRAC facilities are located across the street from the Donnelly Centre, in the C.H. Best Institute.

Dr. Sidhu is a Professor in the Donnelly Centre at the University of Toronto. The Centre provides a highly motivating collaborative environment, as well as access to state-of-the-art equipment, technology, expertise and services. The Sidhu lab is well outfitted with all the equipment necessary for phage display and for protein purification and analysis, including customized robotics for expediting phage selections and screens.

In addition to his primary appointment as a professor in the Donnelly Centre, Dr. Sidhu is also a senior investigator at the Ontario Institute for Cancer Research (OICR) and is cross-appointed in the Department of Molecular Genetics at the University of Toronto.