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Newsletter of the Human Proteome Organization

Current and past HUPOSTs are posted here for your review. Stories, highlights, news, and announcements are gladly accepted for inclusion in the HUPOST. Please submit your information to the HUPO Office at office@hupo.org.

FEATURED ARTICLES


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  • 29 Jan 2021 1:41 PM | Anonymous member (Administrator)

    By Michelle Hill, QIMR Berghofer Medical Research Institute, Brisbane, Australia

    It has been a pleasure to serve as HUPOST editor and HUPO Secretary General for the past 2 years. I would like to thank our staff editor Amanda, HPP and ECR news co-ordinators for their continued dedication to HUPOST and the HUPO community. A highlight for 2020 was the “Proteomics in Action” article series that showcased global proteomics uses in everyday life from forensics, clinical diagnostic, drug development to archeology and marine science. Particular thanks go to Stephen Pennington for his enthusiasm and support, as well as all contributors and the people featured.

    I now pass the reins of HUPOST editor to Ben Garcia. Ben is currently the John McCrea Dickson, MD, Presidential Professor in the Department of Biochemistry and Biophysics, and Director of Quantitative Proteomics at the University of Pennsylvania School of Medicine. His research interests include applying mass spectrometry based proteomics for understanding epigenetic mechanisms in human disease, presenting his work at many HUPO World Congress meetings in the past. Ben has been on the Board of Directors of the United States HUPO since 2011, and served on the HUPO Council since 2016. In addition to his recent election to the HUPO Executive Committee as Member-at-Large, Ben has also joined the Marketing & Membership Committee. Hence, he is well-placed to ensure HUPOST fulfils both HUPO member communication needs and marketing strategies.

    All HUPO members can submit proteomics related announcements (workshops, courses, job openings) for consideration for HUPOST, which is sent out monthly to the HUPO mailing list. If you have any ideas for HUPOST, please reach out to Ben via office@hupo.org.

  • 28 Jan 2021 4:44 PM | Anonymous member (Administrator)

    Emily Hashimoto-Roth is a graduate student at the University of Ottawa pursuing a Master’s in Biochemistry specializing in Bioinformatics, under the co-supervision of Dr. Mathieu Lavallée-Adam and Dr. Steffany Bennett. Having obtained an H.B.Sc. in Biopharmaceutical Science at the University of Ottawa, her current research focuses on the design of statistical models and machine learning algorithms to mine and analyze protein-protein interaction datasets. She is a trainee within the NSERC-CREATE Metabolomics Advanced Training and International Exchange Program (MATRIX), further diversifying her graduate studies. In addition to her studies, she is the Director of Communications for a Canadian federal non-for-profit organization called Pulsar Collective, whose mission is to improve gender equality in STEM. She is also a member of the Canadian National Proteomics Network’s Operations Management Team, which works to advance the proteomics field by fostering a community for researchers to meet and collaborate.

  • 28 Jan 2021 4:34 PM | Anonymous member (Administrator)

    Mathieu Lavallée-Adam, ECR Co-Chair, University of Ottawa, Canada

    The HUPO Early Career Researcher (ECR) Initiative is proud to announce that Dr. Ruth Huttenhain and Dr. Mathieu Lavallée-Adam have been newly elected as its Co-Chairs. The ECR initiative also thanks Dr. Justyna Fert-Bober, founding member of the HUPO ECR Initiative and exiting Chair, for spearheading the activities that the ECR Initiative is now known for, such as the HUPO Mentoring Day, Manuscript Competition and Ph.D. Poster Competition. “I am happy to leave the leadership of the HUPO ECR Initiative in such good hands. I am convinced that Dr. Huttenhain and Dr. Lavallée-Adam will grow the initiative and build an environment that will foster new collaborations and bring new ideas to life,” declares Dr. Fert-Bober. Dr. Huttenhain, who has, among other things, organized the HUPO ECR manuscript competition in the past, says: “In my role as a Co-Chair of the HUPO ECR Initiative, I am particularly excited about growing a larger community of early career scientists in proteomics with the ultimate goal to provide guidance for taking the next steps in their careers. I will also be honored to represent the ECR Initiative in the Organizing Committee of the HUPO World Congress and to advocate for a program that provides visibility for early career scientists and highlights their scientific contributions.” Finally, Dr. Lavallée-Adam, who has been organizing last year’s mentoring sessions at HUPO CONNECT and coordinating ECR’s HUPOST publications adds: “Early career scientists are more diverse than ever and the HUPO ECR Initiative must help them exploit their full potential. I look forward to building upon our current portfolio of activities and constructing new initiatives to showcase proteomics rising stars and provide them the tools to be more competitive on the job market.”

    You will find below short bios of Dr. Huttenhain and Dr. Lavallée-Adam, who are both recipients of the Proteomics Highlight of the Year by an Early Career Researcher Award given at the 2018 Human Proteome Organization World Congress.

    Ruth Huttenhain
    Ruth Huttenhain is an Assistant Professor at the University of California, San Francisco (UCSF) in the Department of Cellular and Molecular Pharmacology. She obtained a Pharmacy degree from the University of Bonn and a PhD from ETH Zurich, Switzerland, where she developed high-throughput, large-scale targeted mass spectrometric approaches. During her postdoc at UCSF, Ruth extended her expertise in quantitative mass spectrometry to study dynamics of protein interaction networks. She pioneered a proximity labeling-mass spectrometry approach that simultaneously captures the precise temporal remodeling and spatial organization of proximal protein networks. The research of Ruth’s research group at UCSF focuses on characterizing protein interaction and signaling networks to understand the biology underlying the development of psychiatric disorders and the sensing and transmission of pain.



    Mathieu Lavallée-Adam
    Mathieu Lavallée-Adam is an Assistant Professor at the University of Ottawa in the Department of Biochemistry, Microbiology and Immunology and is affiliated to the Ottawa Institute of Systems Biology. He obtained a B.Sc. in Computer Science and a Ph.D. in Computer Science, Bioinformatics option, from McGill University. He then performed his postdoctoral research at The Scripps Research Institute. His research focuses on the development of novel statistical and machine learning algorithms for the analysis of mass spectrometry-based proteomics data and protein-protein interaction networks. He also designs computational methods mining proteomics datasets for biological information through their integration with genomics data. Dr. Lavallée-Adam is a recipient of the John Charles Polanyi Prize in Chemistry, recognizing the impact of his bioinformatics algorithms on the mass spectrometry community. He is also a member of the Board of Directors of the Canadian National Proteomics Network (CNPN), in which he mentors a group of early career researchers in the establishment of activities for the Canadian Proteomics community.

  • 12 Jan 2021 3:24 PM | Anonymous member (Administrator)

    Mathieu Lavallée-Adam, University of Ottawa, Canada

    Blandine Chazarin is a postdoctoral scientist in Dr. Jennifer Van Eyk’s laboratory at Cedars-Sinai hospital in Los Angeles, California. After four years in Paul Sabatier University in Toulouse studying Biology, Blandine explored proteomics for a year before beginning a Ph.D., in which she used mass spectrometry to better understand hibernating brown bear physiology, with the goal to discover new therapeutic approaches for muscle atrophy. In October 2019, she obtained her Ph.D. in LSMBO lab in Strasbourg, France. Blandine has also been President of the Youth Club of the Proteomic French Society for three years and was the organizer of yearly meetings dedicated to young scientists in proteomics. She is now involved in the Postdoctoral Scientist Society at Cedars-Sinai and continues to use mass spectrometry to answer biological questions.

  • 12 Jan 2021 2:46 PM | Anonymous member (Administrator)

    Professor Vera Ignjatovic, Chair, HUPO Marketing and Membership Committee

    Vera is a Senior Principal Research Fellow and a group leader of the Haematology team at the Murdoch Children’s Research Institute in Melbourne, Australia. She lead a highly productive, internationally competitive research team in the field of paediatric thrombosis and haemostasis (aka kids' blood). Her research efforts include the use of proteomic studies in the paediatric setting, where she established for the first time the concept of Developmental Proteomics.

    As a lifelong learner she recently completed a Global Executive MBA at the Monash University in Melbourne, an experience that included training in strategic marketing; executive leadership; corporate finance, governance and strategy; as well as innovation and entrepreneurship, and commercialisation of technology. The learnings from the Global Executive MBA and exposure to the world outside of the immediate research environment will be of advantage in her role as the incoming Chair of the HUPO Marketing and Management Committee.

    Whilst the 2021 Marketing and Membership committee is in its infancy, Vera is very happy to announce 5 new committee members, James Waddington (Co-Chair), Conor McCafferty (PhD representative), Jennifer Geddes-McAlister, Benjamin Garcia and Lennart Martens. She very much looks forward to working with all HUPO Marketing and Membership Committee members to increase the visibility of the HUPO brand in 2021 and beyond.

  • 26 Nov 2020 6:01 PM | Anonymous member (Administrator)

    Mathieu Lavallée-Adam, University of Ottawa, Canada

    Emily Hashimoto-Roth is a graduate student at the University of Ottawa pursuing a Master’s in Biochemistry specializing in Bioinformatics, under the co-supervision of Dr. Mathieu Lavallée-Adam and Dr. Steffany Bennett. Having obtained an H.B.Sc. in Biopharmaceutical Science at the University of Ottawa, her current research focuses on the application of statistical models and machine learning algorithms to mine and analyze protein-protein interaction datasets. She is a trainee within the NSERC-CREATE Metabolomics Advanced Training and International Exchange Program (MATRIX), further diversifying her graduate studies. In addition to her studies, she is the Director of Communications for a Canadian federal non-for-profit organization called Pulsar Collective, whose mission is to improve gender equality in STEM. She is also a member of the Canadian National Proteomics Network, which works to advance the proteomics field by fostering a community for researchers to meet and collaborate.

  • 30 Oct 2020 11:43 AM | Anonymous member (Administrator)

    Once again this year, the HUPO Early Career Researcher (ECR) initiative in collaboration with the EuPA Young Proteomics Investigators Club (YPIC), organized mentoring activities during HUPO Connect 2020, where early career researchers could hear from and interact with leaders of the Proteomics field. This year, the mentoring sessions were integrated in the main program of the congress at different time slots to allow people across to globe to connect and exchange. In the first session, trainees and supervisors learned how to get the best out of a mentor-mentee relationship with Lisa Jones (University of Maryland) and Brandon T. Ruotolo (University of Michigan). In the second session, Benjamin Garcia (University of Pennsylvania), Ruth Huettenhain (University of California San Francisco), and Justyna Fert-Bober (Cedars-Sinai) discussed work-life balance and the challenges faced during the COVID-19 pandemic. Finally, in the last session, Bernard Delanghe (Thermo Fisher Scientific) and James Anson (Molecular Omics) gave insights about the transition from academia to the industry.

    With over 200 attendees participating in all three sessions, the 2020 mentoring activities show the greatest attendance since the beginning of mentoring activities at the HUPO conferences. We thank all mentors for sharing their experience with mentees. We also thank all attendees for their participation and for engaging in stimulating, thought provoking discussions during the congress.

  • 30 Oct 2020 11:40 AM | Anonymous member (Administrator)

    The HUPO Early Career Researcher (ECR) initiative and the EuPA Young Proteomics Investigators Club (YPIC) held a virtual poster session at HUPO Connect 2020 for the finalists of the 2020 Ph.D. poster competition sponsored by Molecular Omics. Eight abstracts were selected by an international panel to give their authors an opportunity to present their work in 5-minute oral presentations during a dedicated Ph.D. Poster Competition session at HUPO Connect 2020. The eight finalists were: Edwin Escobar, University of Texas at Austin, Austin, United States; Xiaobo Tian, University of Groningen, Groningen, Netherlands; Joshua Charkow, University of Toronto, Toronto, Canada; Ugo Dionne, Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec, Canada; Andikan Nwosu, Brigham Young University, Provo, United States; Maria Jassinskaja, Division of Molecular Hematology, Lund Stem Cell Center, Lund University, Lund, Sweden; Ana Montero Calle, Functional Proteomics Unit, UFIEC, Chronic Disease Programme, Instituto de Salud Carlos III, Madrid, Spain and Jessica Nickerson, Dalhousie University, Halifax, Canada. All finalists gave very high-quality presentations, which made for an extremely interesting session. In the end, Ugo Dionne took 1st place ($300), Maria Jassinskaja finished 2nd ($150), and Edwin Escobar was recognized with the 3rd place ($150). Congratulations to all finalists! You can read more about the finalists here.

  • 30 Oct 2020 11:35 AM | Anonymous member (Administrator)

    The HUPO Early Career Researcher (ECR) initiative and the EuPA Young Proteomics Investigators Club (YPIC) joined forces for HUPO Connect 2020 to organize the sixth edition of the ECR manuscript competition to select the Proteomics Highlight of the Year by an early career researcher. Every year, early career proteomics researchers are invited to participate to this competition by submitting a manuscript they published in the previous year. An external committee then selects three finalists, who present their work at the HUPO World Congress. Their talks are then evaluated to determine the winner of the competition.

    This year's finalists were Marian Kaloscay (Harvard Medical School) Maria Robles (Ludwig Maximilian University of Munich), and Jakob Trendel (Technical University Munich). The dedicated oral presentation session for the manuscript competition was one of the highlights of HUPO Connect 2020 with three high-quality talks followed by dynamic Q&A sessions. The quality of the presentations made it very difficult for the panel of external judges to select the overall winner of the competition. Ultimately, this year’s Proteomics Highlight of the Year by an early career researcher was awarded to Maria Robles for her work entitled: “Sleep-wake cycles drive daily dynamics of synaptic phosphorylation”. Congratulations to all! You can read more about the finalists here.


  • 29 Sep 2020 3:36 PM | Anonymous member (Administrator)

    By Michelle Hill, QIMR Berghofer Medical Research Institute, Brisbane, Australia, and Stephen Pennington, University College Dublin, Dublin, Ireland.

    Developing new therapies for clinical use is a long and costly process. Optimizing dose and schedule in early clinical trials and selecting the right patients for the therapy are two critical aspects for the drug development process. Read how Dr Henrik Neubert (Pfizer), Dr Amanda Paulovich (Fred Hutchinson Cancer Research Center) and Dr Carl Barrett (Astra Zeneca) have used targeted proteomics to facilitate drug development.

    In the words of Dr Carl Barrett (Astra Zeneca), “90% of drugs fail for 2 reasons, bad chemistry or bad biology”. Protein technologies have been central in drug development, as most drug targets and their downstream effectors are proteins. In recent years proteins (often antibodies) are also being used as new therapeutics. Recently, proteomics technologies have matured to the stage where they are now sufficiently robust and reproducibly that they being developed into robust high throughput assays. Proteomics can be key to helping to identify bad chemistry (of the drug), and to illuminate bad biology by facilitating pharmacodynamic (PD) and proof of mechanism (POM) studies.

    Selecting therapeutic targets with the right properties

    With PhD and postdoctoral training in quantitative protein mass spectrometry, peptide synthesis and MALDI surface chemistry, it was natural for Dr Hendrik Neubert to bring his proteomics knowledge to drug development when he joined Pfizer in 2004. Hendrik now leads a translational biomeasures and protein biomarkers group that develops proteomics assays based on mass spectrometry to measure synthesis rates and concentrations of therapeutic targets as well as their engagement with biotherapeutics. This proteomic data when combined with critical experimental data enables mechanistic modeling to support key drug development program decisions such as the feasibility of modulating the activity of a particular protein target or establishing drug dosing regimens. Hendrik and his team have been particularly influential in the area of immunoaffinity mass spectrometry and worked to robustly position this technology in early clinical trials of Pfizer’s drug candidates. His team was the “terminator” for Pfizer’s osteopontin neutralizing antibody program due to undesirable target properties.

    Osteopontin seemed to be a perfect drug target and it was being pursued by several biopharmaceutical companies. It is a circulating protein and pre-clinical studies implicated it in many immune-related diseases, liver fibrosis and cancer. In a cynomolgus monkey model, a neutralizing antibody to osteopontin was effective in ameliorating arthritis. The literature describes a successful phase I trial demonstrating safety and tolerability in men, however, no improvement in disease was observed in a subsequent Phase IIA trial on rheumatoid arthritis.

    The Pfizer team was interested in developing a neutralizing antibody against osteopontin for a different indication but before proceeding, Neubert’s team was tasked to investigate the potential PK/PD risks associated with the osteopontin target. The team realized that the half-life of osteopontin in human blood had never been determined before. This is an important parameter for a neutralizing antibody, because if osteopontin protein is quickly eliminated from the body, then the amount and frequency of antibody dosing required for efficacy may not be feasible therapeutically.

    Protein half-lives were previously measured by injecting radioactively or fluorescently labelled recombinant protein into preclinical models. Unfortunately, this method is really inadequate for a reliable physiologically relevant half-life measurement as it only measures the rate of elimination, the protein being measured is not endogenous and is typically administered above endogenous concentrations. Most importantly the approach cannot be applied to humans!

    With their proteomics expertise, Neubert’s team used longitudinal serum samples from a previously conducted stable-isotope labelled leucine (13C-Leu) pulse-chase study in humans and enriched osteopontin using an anti-osteopontin antibody prior to tryptic digestion. Liquid chromatography-tandem mass spectrometry of a proteotypic peptide with and without 13C-Leu incorporation was used to determine the half-life of osteopontin in human blood from healthy individuals. Surprisingly, with a half-life of around just 20 minutes osteopontin has one of the shortest half-lives Neubert’s team has ever observed for a human protein. Considering the rapid synthesis and clearance from human blood it was evident that the dosing schedule for a neutralizing antibody that would be required was simply not feasible. Hence, Pfizer stopped the discovery project very early before significant further investments were made. Of course, pharma teams all want their therapeutic programs to be successful, but if a drug development program does fail it is ideal it fails early to avoid costly clinical studies so resources can be spent on programs that are more likely to succeed.

    Elucidating tumor biology and drug mechanisms of action

    Quantifying proteins and protein networks for pharmacodynamic and proof of mechanism studies is critical for translating novel therapies, to confirm the biological mechanisms underlying new compounds and to inform drug dose and scheduling in clinical trials. Immunohistochemistry (IHC) is generally the preferred technology for these studies because it is sensitive, provides biomarker spatial distribution and is semi-quantitative. For clinical implementation, IHC is a well-understood analytical modality. However, IHC is critically dependent on the absolute specificity of individual antibodies, and establishing this specificity is costly in terms of time and resource. As a result, only a handful of fully validated IHC protocols can be developed for each drug project, where the choice of which IHC assays to develop is largely done on the basis of “best educated guess” arising from orthogonal preclinical methods such as Western blotting.

    Adding to the challenge of measuring specific proteins by IHC, it is recognized that proteins act as interconnected networks, and the effects of cancer driver mutations for example spread throughout the networks. Ideally we would have assays to quantify panels of multiple proteins in early phase clinical trials to assess the activity of pathways/networks that determine treatment responses, and this developmental effort is not practical using IHC

    More specific and quantitative “NextGen” proteomic techniques are now starting to be used, exemplified by the stimulating interdisciplinary collaboration between Dr. Carl Barrett (AstraZeneca) and Dr. Amanda Paulovich (Fred Hutchinson Cancer Research Center). Paulovich is a geneticist and oncologist who has run a translational proteomic laboratory at Fred Hutch for the past 17 years. Barrett has a PhD in biophysical chemistry and is VP Translational Sciences Onc iMed at AstraZeneca.

    A recent collaborative project between their teams identified phospho-RAD50 as a novel pharmacodynamic biomarker for inhibitors of DNA damage checkpoint signaling kinases ATM and ATR, which are being tested in clinical trials in a variety of cancers. While pharmacodynamic biomarkers were available, the assays and biomarkers were not ideal.

    Paulovich’s lab developed a multiplexed immuno-multiple reaction monitoring mass spectrometry assay to measure proteins and phosphoproteins in the signaling cascade downstream of the DNA damage checkpoint. The team used this targeted mass spectrometry-based assay panel to identify Ser635-phosphorylated RAD50 as a novel pharmacodynamic biomarker of ATR and ATM kinase inhibitor pharmacology. The pRad50 biomarker was further validated by Barret’s team using two preclinical xenograft models and using archived human tumor material. Together this supported clinical utilization of pRAD50 as a biomarker to probe clinical pharmacokinetic/pharmacodynamic relationships, thereby informing recommended Phase 2 dose/schedule.

    Towards broader clinical testing

    The productive interdisciplinary academia-pharma collaboration between Barrett and Paulovich has propelled immuno-MRM assays from research to established Clinical Laboratory Improvement Amendments (CLIA)/clinical grade assays, suitable for clinical trials to facilitate drug development. Paulovich’s team has developed >1,400 targeted mass spectrometry-based assays, which her laboratory runs in its recently-established CLIA environment. CLIA establishes the quality laboratory framework for human diagnostic testing, so Paulovich is taking targeted proteomics assays a step closer to clinical use.

    Barrett and Paulovich are actively involved with the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), a national effort to accelerate the understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis, or proteogenomics. A major goal of CPTAC is to translate proteomic technologies into clinical use. To facilitate distribution and uptake of proteomic technologies by the community, CPTAC has developed public resources, such as the CPTAC Assay Portal and the CPTAC Antibody Portal. One of the CPTAC antibodies is incorporated into a clinical thyroglobulin mass spectrometry test, which is used for thyroid cancer patients with autoantibodies that interfere with widely used immunoassays.

    The specificity, sensitivity and robustness of targeted proteomics assays make them highly attractive for clinical trials where thousands of samples require analysis using validated methods. Indeed, Neubert’s team are now using targeted proteomics assays not only to assess the effect of biotherapeutics but increasingly also to examine transgene protein expression in gene therapy studies, both preclinically and clinically.

    Interested to know more? Register for HUPO Connect 2020 to hear exciting scientific presentations from both Hendrik Neubert and Amanda Paulovich as well as other global leaders.

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