Matthew Engel

This May I published a paper in the journal Biochemistry with my previous lab group at Brookhaven National Laboratory. The publication is about the development of a new platform technology for high-throughput protein crystallography which has potential to greatly accelerate the field of structure-based drug discovery. We analyzed protein crystals using x-ray diffraction at the National Synchrotron Light Source (NSLS) and Advanced Photon Source at Argonne National Laboratory. X-ray crystallography is important because it can reveal the atomic three-dimensional structure of proteins, which allows scientists to visualize where drugs bind and how they work on the molecular level. This is even helpful for discovering new drugs and understanding how things like proteins function in the body.

Front-page of the Biochemistry website featuring our article

What was unique about our experiment, was that we transported very tiny protein crystals (microcrystals) through the air using sound waves. To do this I went to California and used a special instrument called the Echo Liquid Handler, manufactured by Labcyte, Inc., which uses acoustic drop ejection to rapidly dispense nanoliter droplets of fluid.

The Department of Energy is currently building a new light source where I work at Brookhaven National Laboratory called NSLS-II for $912m which will come online in 2014. This technology we developed in this paper should help speed up the process for data collection at the new NSLS-II.

A key figure in our paper showing nanoliter droplets of fluid being dispensed (A). The droplets we created contained microcrystals, which were then shot onto the Kapton mesh (B). These samples can be diffracted at the beamline (C) and used to solve the structure of proteins.

Organized by the Fundamentals of the Bioscience Industry Program – Alumni Executive Committee

Presenting:

Integrating personalized health care into clinical practice Organized by: Fundamentals of the Bioscience Industry Program: Alumni Network Executive Committee NY State Center for Biotechnology Mount Sinai School of Medicine Date: Thursday, December 2nd, 2010 at 6:30pm Location: Mount Sinai School of Medicine, Icahn Medical Institute 1425 Madison Avenue (@ 98th St.), 1st Floor Seminar room Click Here to RSVP View Our Website Abstract The pursuit of personalized medicine continues to transform biomedical research and innovation from the bench to the bedside. Fundamentals of the Bioscience Industry Program (FOBIP) Alumni Network Executive Committee‘s Personalized Medicine Seminar brings together a clinical scientist and two healthcare experts to discuss, debate and identify the current challenges and opportunities for the development of a personalized approach to medicine and healthcare. They will provide perspective from the different participants of the healthcare industry and offer insights into this promising area of medical research. Panelists Paul Chapman, MD, Professor of Medicine of Weill Medical College and Graduate School of Medical Sciences, and Attending Physician of Memorial Sloan-Kettering Cancer Center, and Memorial Hospital for Cancer and Allied Diseases. His research interests include the evaluation of drugs that target the genetic mutations in melanoma cells. Mark Horn, MD, MPH, Chief Medical Officer of Target Health, Inc., and Senior Advisor to Avalere Health. Prior to joining Target Health, Dr. Horn spent 25 years at Pfizer Inc., leading teams in Licensing & Development, Medical Marketing in multiple therapeutic areas, and Worldwide Public Affairs and Policy. Glen Park, PharmD, Senior Director Clinical and Regulatory Affairs of Target Health, Inc. Dr. Park has over 20 years of extensive regulatory affairs and clinical development experience acquired in industry – Aventis Pharma, Ingenix Pharmaceuticals, and Sankyo Pharma, and academic settings – University of Iowa and University of Toledo. Moderator Eric Vieira, PhD, Assistant Director of the Office of Technology & Business Development of the Mount Sinai Medical Center, and Course Director of the Fundamentals of the Bioscience Industry Program. Agenda: 6:30 pm ? 8:00 pm Panel Discussion (networking reception to follow)

Minimally Invasive Delivery of Mesenchymal Stems to the Nucleus Pulposus Using an In Situ Thermoresponsive Hydrogel

In July 2009, I passed a major milestone in my graduate research in the Department of Biomedical Engineering at Stony Brook University – I passed my qualifying exam! This literally required hundreds and hundreds of hours of work, during which I read over 50 scientific publications and synthesized them to come up with an original grant proposal. In this case, my challenge was to use a tissue engineering approach to treat degenerative disc disorder. Below, I will place my statement of interest plus a copy of the grant proposal and presentation I made. I most definitely learned a tremendous amount from this process, most of which I will be keeping private and storing away for later use. But it really teaches you how to make an effective presentation and to prepare thoroughly for a talk.

In a nutshell, the project focuses on stem cell implantation technology to treat spinal chord injuries associated with aging, and could also be applied to acute injuries.

Click on individual slides to see the full image

PROJECT SUMMARY: This proposal aims to design an in situ curable hydrogel composed of PNIPAAm-PEG capable of delivering therapeutic cells and drugs to the degenerated nucleus pulposus (NP) of an intervertebral disc (IVD). The therapeutic cells will be human mesenchymal stem cells (hMSCs) differentiated into NP-like cells by exposure to hypoxic low oxygen conditions in the presence of transforming growth factor β1 (TGF- β1). The hydrogel is composed of a solution containing 10% PNIPAAm-PEG(8000) at a 1:1600 ratio of PNIPAAm:PEG which undergoes a sol-gel transition at physiological temperatures (32°C). Modifications to the PEG molecular weight or concentration can be used to alter the hydrogel stiffness or sol-gel transition temperature. These properties will allow users to prepare cell and drug loaded solutions at ambient temperatures and then inject them into the degenerated disc, at which point they solidify in situ. The hydrogel is capable of being blended with small molecule inhibitors of nitric oxide synthase (NOS). The inhibition of NOS has been shown to increase proteoglycan content which can restore disc height to the degenerated IVD.

Download copy of grant proposal here (.pdf)

Today the Atlantic is reporting in an interesting article about the regional growth of patent filings in the United States. The article segregates the distribution of high-tech industries in the US by number of patents issued, an important measure of regional economic growth and technology commercialization. The data, provided by the Martin Prosperity Institue in Toronto shows that the classic industrialized regions of the US including Pittsburgh and Detroit have fallen precipitously off the map, while unsurprisingly, regions like Silicon Valley, CA and Houston, TX show significant growth in intellectual capital. New York state saw large growth in the 1990′s but has since declined in overall patent filings. With the development of new technology commercialization programs at the university centers such as the New York State Center for Biotechnology at Stony Brook University, hopefully we will begin to see growth in terms of new patents issued and licenses granted to private industry which would indicate true commercial growth. I would be extremely interested to see the distribution of patent filings by industry such as the computer software development, electrical engineering, pharmaceuticals and biotechnology sectors.

This year I have had the distinct proviledge of attending the Rapidata 2009 Course at Brookhaven National Laboratory. Organized by Robert Sweet, Alexei Soares, and many others, Rapidata 2009 has been a tremendous learning experience focusing on the practical aspects of protein crystallography (PX). Over the last 24 hours I have met students and faculty from Harvard, MIT, Rockefeller, Providence, Purdue, Oxford, Sweden, the Netherlands, Brazil and Switzerland. It is truly a gathering of some of the best crystallographers in the world who are the globe’s leaders in cryo-cooling, structure solution, phasing, software development and beamline operations. The week long program features lectures and hands on tutorials where students can bring actual samples from their home laboratories, collect data from them and solve the structure at the NSLS. I will be working on a previous data set containing multiwavelength anomolous diffraction (MAD) data and try to solve its structure. I hope to report back from the course with more details later this week.

A streaming video can be found here on the bottom of this webpage.

The full presentation was uploaded onto the BNL website, and I have a copy of it here. Below, I will share some of the slides which I thought were most critical and relevant; as each could warrant a full discussion unto itself. One of Chu’s goals was to establish the idea that our world is changing. Many peoples are not prone to understanding these types of changes, or how they will affect society. However, it is important not to ignore them but study them and try and calculate how they will impact humanity. One may ask ‘Will these changes be beneficial or detrimental? Can we alter their course, can man control them? Are these changes to our world caused by man, or a byproduct of our society?’ Chu establishes three ‘myths’ which are commonly thought to be true, and present evidence to combat each myth. They are:

1. The wealth of a country is proportional to the energy it uses and its carbon footprint.
2. Energy efficiency and CO2 reductions are not affordable.
3. We have all the technology we need to solve the energy problem. It is only a matter of political will.

The graph above shows the development index of many nations in the world including the U.S., Japan, France, Netherlands, Germany, Israel etc. in proportion to their energy consumption. From here, we can see that many developed nations all across the world are able to maintain a high standard of living while having much lower energy consumption per person. Therefore, in America we have the potential to maintain or even raise our standard of living while lowering our energy consumption – this data shows that it can be done.

Here we see the energy consumption in the United States per person in kWh compared to the energy consumption in California per person. It is obvious, there is a drastic difference between the two. The average person in California uses much less energy than the average person in the U.S. Even while the per capita GDP in California doubled, its energy consumption remained flat. This was due to greater energy efficiency practices, that we could learn from. These practices would reduce our dependence on foreign oil and help reduce pollutin emissions.

I will post this now, but continue updating it over the weekend. Enjoy, and best wishes.