Barnett Institute News

John R. Engen Featured in Analytical Chemistry
The Oct 1 issue of Analytical Chemistry leads with a cover story by Prof. John Engen on Analysis of Protein Conformation and Dynamics by Hydrogen/ Deuterium Exchange MS. This feature article is an update on the rapid progress, emerging applications, and current challenges of HX-MS.
Read the article; Download the podcast; Visit Engen's HX MS website

The 2009 Barnett Lectures.
Richard D. Smith presented the 2009 Barnett Lectures "Advances in Proteomics for Biomarker Discovery and Validation" on September 23. Protein biomarker discovery strategies at present either provide insufficient throughput to adequately account for biological and other sources of variation, or allow only very limited coverage of potential biomarker candidates. Dr Smith presented developments that address this limitation, including Accurate Mass and Time tags (AMT), Unique Sequence (US) Tags and Ion Mobility Spectrometry (IMS) which together enable mass spectrometric (MS) proteomics measurements that are of much higher throughput and and overall data quality.
  Dr. Smith is a Battelle Fellow and Chief Scientist in the Biological Sciences Division, and Director of Proteomics Research, at Pacific Northwest National Labs (PNNL) in Richland, WA.
Summary and Pictures

The 2009 Francine and Michael Saferstein Memorial Lectures in Forensic Science:
Paul C. Gianelli, J.D., of Case Western Reserve University, was selected to discuss "Developments in Forensic Science" for the 2009 Saferstein Lectures. There has been a paradigm shift in the way courts deal with exxagerated expert testimony of foresic evidence in criminal cases. DNA testing revolutionized forensic science not only with its accuracy but by providing a quantitative evaluation of its uncertainty, in contrast to historical methods such as handwriting comparisons or fingerprints. This year's Saferstein Lectures illustrate the findings of the 2009 National Academy of Sciences Report on forensic science, in terms of specific cases where methods have been well or ill used, and concludes with recommendations how scientific method can further improve jurisprudence.
  Prof. Gianelli is the Albert J. Weatherhead III and Richard W. Weatherhead Professor of Law at Case Western Reserve University. He is a well-regarded expert and prolific author on the topic of scientific evidence, cited in decisions of the U.S. Supreme court. He has served as Reporter for the American Bar Association (Criminal Justice Standards on DNA Evidence) and co-chair of the ABA Ad Hoc Commiittee on Innocence. Summary and Pictures

Short Course in State-of-the-Art Protein Analysis and Regulatory Science
From Aug 31, the Institute convened a four day intensive course, highlighting modern protein analysis methods which are applicable to biopharmaceuticals and relevant to the regulatory approval process. Students were introduced to the state-of-the-art in separations, mass spectrometry, carbohydrate analysis and protein degradation pathways. The faculty included Keith Webber, Deputy Director of the Office of Pharmaceutical Science, CDER, FDA; Pauline Rudd of the Conway Institute in Dublin; and Robert Garnick, formerly Senior Vice President of Regulatory, Quality, and Compliance at Genentech; in addition to Barnett Institute Faculty Fellows. Additional information on the course can be found on the event website at http://www.northeastern.edu/cas/barnett.html. (photo gallery)

Dr. Karger lecturing (left); the class (center); Res. Asst Prof. Billy Wu with Annie He of Momenta.

Barnett Institute Featured in C&E News Cover Story
   The Chemical and Engineering News article "Analyzing Protein Drugs: Scientists Devise New Streamlined Methods to Understand the Complexity of Biopharmaceuticals", highlights a number of Barnett Institute researchers and methods. Also featured is the Center for Advanced Regulatory Analysis (CARA), which aims to transfer analytical techniques from the basic research stage to the drug development arena.
    The article, motivated by the size of the biotech market (over $90 billion in 2008) and the potential impact of biosimilars, describes how the safety and efficacy of protein drugs is intimately tied to post-translational modifications –"how [proteins] are processed and folded by cellular machinery .. and how processing conditions may yield different modification patterns or impurities".   Fully half of the article describes methods in late development at the Barnett Institute, including work using CE/MS to locate glycans, in partnership with Momenta Pharmaceuticals, and using a combination of ETD and CID fragmentation with MS to identify disulphide bridges and detect disulphide scrambling. The article also highlights how Prof. Engen's hydrogen/deuterium exchange can address questions about overall protein structure, in a collaboration with Waters Corp, and Prof. Hancock's demonstration that glycan structures can serve as a molecular fingerprint to identify exactly who manufactured a specific protein. The article concludes with two important questions that drive much of our work: how to tell whether something analytically significant is also clinically significant? And what key properties are scientists currently missing, in analysis of biologics? (7/20/'09)

Claude Eon, and his stellar career with the French Ministry of Defense, exemplify the value of learning to apply chemistry, over merely learning chemistry. Dr. Eon did postdoctoral work with Dr. Karger in the early 1970s, and visited the Institute recently.
Few could have better insight on science-in-society and the duties of scientists as citizens. In his 23-year career with the Ministry, he has been a scientific advisor for international disarmament issues, directing large R&D programs in NRBC (nuclear, radiological, biological, and chemical) defense and homeland security, environmental and safety technologies, and disposal of old ammunition. He still serves as Advisor to the Armament National Council (Military Reservist) as a chief engineer of the Armament Corps of Engineers.

"I believe the pre-eminence of lawyers and businessmen is waning. Scientists are good people, not overly greedy; on the contrary, relatively disinterested — but exceptionally well-trained thinkers. Above all, they tell the facts!!   Although modesty is crucial, because nobody knows the absolute truth, I found that scientists tend to be a bit too shy on this score. They should not remain distant spectators but, if the occasion presents, should voice up as concerned (and often very knowledgable) citizens. What I would like to convey to all young students and readers is ..." (more) (7/16/'09)

Collaboration on AIDS glycans with Ragon Institute
Prof William Hancock has entered into a collaboration with the newly formed Phillip T. and Susan M. Ragon Institute of MGH MIT and Harvard. Together, they are investigating changes in cell-surface glycoproteins that accompany AIDS infections, motivated by the possibility of producing an AIDS vaccine targeted to these changes. The Barnett Institute was selected for this collaboration based on Dr. Hancock's expertise in clinical glycoproteomics, and for state-of-the-art LC-MS methods developed here which can determine glycan structural changes in greater detail, from smaller clinical samples. (see NU News for more information) (7/8/'09)

Q&A on Biosimilar Pharmaceuticals The Northeastern Voice interviewed Prof. Karger on the difference between generics and biosimilars, and the role of the upcoming Center for Advanced Regulatory Analysis to ensure drug safety, quality, and competitive costs. (see the Voice interview) (7/8/'09)

Shiaw-Lin (Billy) Wu with Prof. Barry Karger

2009 Hoehn Lectures, on Metabolomics.
  On May 4, the Institute hosted the tenth annual Dieter and Inge Hoehn Lectureships. This year's theme, Metabolomics, was addressed first from an industrial perspective by John Ryals, President and CEO of Metabolon, Inc. (Durham NC) with a presentation "The Use of Biochemical Profiling for Biomarker Discovery". Metabolon developed technologies which can profile up to 2000 different compounds in sera, with high sensitivity and reproducibility, using LC-MS methods with judicious quantitative standards. It is active in numerous collaborative projects with public health programs and the pharmaceutical industry.
   The second lecture, "The Symbiotic Evolution of Mass Spectrometry and Human Health" was presented by Gary Suizdak, Senior Director of the Scripps Center for Mass Spectrometry and Professor of Molecular Biology at the Scripps Research Institute in LaJolla. Prof. Suizdak developed METLIN, a metabolite database containing over 15,000 structures, with a data management system to assist in metabolite research and identification. (photo gallery) (5/5/'09)

Prof. Vouros presenting certificates to Gary Suizdak and John Ryals; John Ryals presenting; Dieter Hoehn and Gary Suizdak.

Graduate Student Wins AHA Student Fellowship
Tianzhu “Indi” Zang, a third-year graduate student with Sunny Zhou, recently won a two-year predoctoral fellowship from the American Heart Association for his project “Protein Modifications and Crosslinking by Homocysteine Thiolactone in Cardiovascular Diseases.” (more) (6/15/2009)

(also honored in Northeastern News)

Dr. Mark Mamula, Professor of Medicine at Yale University, described how modifications to proteins can break immune tolerance to "self" proteins, in a special lecture "Protein Modifications in Biology and Medicine" (more)(2/18/2009)

Mark Mamula with Sunny Zhou

The 2009 Molecular Bioseparations (MSB) Meeting Feb 1-5 in Boston was the 20'th anniversary of the founding of these annual meetings by the Barnett Institute. Established as HPCE in 1989, marking the date capillary electrophoresis branched off from the HPLC community, the meeting changed its name to Molecular Scale Bioseparations in its second decade, as interest and attendance expanded in the related techniques of capillary electrochromatography and microfluidic devices.
     The Institute maintains a high level of participation in the meetings. This year's program included nearly a dozen presentations by Institute members, alumni, and affiliates, from Dr. Karger's opening keynote address “Follow-On Biologics - New Challenges and Opportunities for LC/MS and CE/MS” on Sunday evening, to Frantisek Foret's closing plenary lecture on Thursday afternoon. Andras Guttman and Tomas Rejtar spoke in the Carbohydrates session Tuesday morning; and Roger Kautz on using droplet microfluidics for NMR in the Detection session on Thursday. Alumni Iulia Lazar, (bio-omics), Karel Kleparnik (nanoscale), Oscar Salas-Solerno and Wassim Nashabeh (CE in Biotech),also presented or chaired sessions. (See photo galleries of the conference.) (RAK 2/6/2009)

Dr. Karger receiving a congratulatory cake from 2009 MSB program chair Jonathan Sweedler.

Barnett Institute Celebrates 35'th Anniversary.
   At a gala celebration on October 18'th, the Barnett Institute celebrated its 35'th anniversary with faculty and friends, including President Aoun and many members of the Barnett family. Reflections on the decades toasted the many alumni, faculty and staff that have reinvented the Institute so many times.  Future expectations were presented with the first installment of the Barnett family's gift to launch the Center for Advanced Regulatory Analysis.  (more)

Barnett Institute Receives $3M Donation to Launch Drug Regulatory Analysis Center
The Institute has received a leadership gift from Louis Barnett and his family.   The $3 million donation includes a $1 million challenge grant from the Barnett family, whose 1983 endowment gift is responsible for the name of the Barnett Institute.  The gift will help launch a new Center for Advanced Regulatory Analysis (CARA), including a GMP/GLP Laboratory.  Devised in collaboration with leaders of the biotechnology industry, CARA will play a critical role in ensuring drug safely and quality for consumers, focusing on the regulatory analysis of biotechnology products. The GMP/GLP Regulatory Laboratory will validate methods developed in the research arm and conduct regulatory analysis. (more) (9/30/08)

At the October 17 meeting of the Strategic Advisory Board: (from left) Steve Zoloth, Bob Matz, Saul Kurlat, Dan Levangie, Louis Barnett, James Waters, Barry Karger, Rob Garnick, Laurie Werner, and Dieter Hoehn.  (not pictured:  Eliot Barnett, Peter Barrett).  (more on the Strategic and Scientific Advisory Boards)

Mary Alice Hefford (Health Canada), on Philosophy and Practice of Research to Support Regulation of Subsequent Entry Biologics.  
Dr.  Hefford heads the Centre for Biologics Research (CBR) of Health Canada, which develops methods for evaluating therapeutics and advises their evaluators.  Dr. Hefford described the unique role of regulatory research and its distinctions from basic, applied, or academic research.  Regulatory analysis is performed in the context of determining comparability of the therapeutic effects of two products, rather than their chemical identity.  She presented examples of physicochemical methods in use (FTIR, CD, LC, CE, NMR, MS) and discussed the analytical limitations of evaluating a formulated drug product, rather than the pure drug substance.   In her conclusions, she described work in progress to enable and incorporate Quality by Design.  (summary of the presentation) (10/7/2008)

Recent Headlines   (Archived News Stories)
   James Paulson on Functional Genomics ( 2008 Barnett Lectures)
   New Adjunct Professors:  Peter Barrett and Rob Garnick
   Prof. Barry Karger Receives Bergmann Medal, Horvath Medal,
     appointed to Hungarian Academy of Sciences
   Institute Hosts Biogenerics2008 Conference
   Prof. Hancock Leads trans-NIH Alliance of Glycobiologists 
      for Detection of Cancer and Cancer Risk
  
   Barnett Institute Awards Ceremony
   Barnett Institute to host Biogenerics Conference

Recent Papers    (Recent Papers List)

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