Tuesday
Aug132013

Smashing atoms and taking pictures: my experiences at the Martinos Center Radiopharmacy.

I’m Chris Moseley and I am a former radiopharmacy technician and founding member of the Martinos Center for Biomedical Imaging PET production facility. I joined MGH in 2011, just prior to the tracer facility becoming operational. Like many fresh college graduates (or students for that matter) I had few, if any, appreciable skills. But I did have an expensive piece of paper and a dream to build something more for my future self. I contacted Dr. Jacob Hooker looking for a position in his lab and was pleasantly surprised to get a response. Despite him freely agreeing to the aforementioned assessment of my utility, he conceded to my enthusiasm and determination and offered me a job. Two years later I had written and coauthored over half a dozen publications including a first authorship for a chapter in a textbook, worked with some of the world's finest physicians and scientists, and realized my wish to enter medical school. The following is an account of what life was like for me at the radiopharmacy and of what Dr. Hooker was able to do for me as an employer, mentor, and person.

I was ecstatic to join the juggernaut collaboration between Massachusetts General Hospital, Harvard University, and Massachusetts Institute of Technology. The Martinos Center has an abundance of material and intellectual resources, uniting to create an environment that fosters innovation and makes definitive progress. Whereas I had been accustomed to associating labs with mediocre equipment repurposed until it became more duct tape than machine, I now worked in a facility outfitted with cutting edge and occasionally "prototype stage" technology. On any given day I operated a particle accelerator, chemical synthesis machinery, a full quality control lab, and blood analysis robot. Using these tools, I was able to participate in the development of novel molecules. It was remarkable to watch the evolution of a compound synthesized by Dr. Hooker's chemists as it developed from cold to "hot" chemistry and to the eventual injection into a living organism. I cannot emphasize enough the uniqueness of this opportunity. I was literally offered a chance to take part in every piece of the research effort including drug development, equipment engineering, imaging analysis, pharmacokinetic modeling, and more things I can't recall. Leading me in each of these ventures were some of the most gifted and world renowned scientists in fields including chemistry, biology, neuroscience, radiology/imaging, engineering, biophysics, computational sciences, and so on. Furthermore, I was encouraged to propose my own research projects, with the full resources of the center at my disposal.

Despite the fantastic research environment my ultimate goal was to attend medical school. Having unsuccessfully applied to medical school in the past, Jacob helped me to formulate and execute a plan to improve my application and put me in touch with prominent physicians. It was a boon to interface with physician scientists, of which MGH has no short supply. I began a project with a neuro-oncologist to assess treatment outcomes for malignant brain tumors by using a radioactive form of a 'standard-of-care' chemotherapeutic. For my part in this collaboration, I was tasked with producing the radioactive compound, which was no trivial matter. Along with the very talented post-docs in Dr. Hooker's lab, I improved the synthesis of this drug, and I wrote my first publication as a first author. As an added bonus, I was able to shadow the neuro-oncologist in the clinic, where I met fascinating patients and learned a tremendous amount about people coping with terminal diseases. Professionally, this meant I could add another letter of recommendation to my application package as well as plenty to write about for my admissions essays. Personally, I was able to experience medicine in a fashion that I had been otherwise unable to explore and ultimately this understanding galvanized my desire to become a physician. I believe this was apparent during my medical school interviews, when I recounted these events, and was instrumental to me gaining acceptance to multiple medical colleges and tens of thousands in scholarships.

To give a fair warning to those interested in attaining a graduate education, the fun doesn't stop once medical school starts. In the first week students are coached on how to prepare for the next step in medical training, residency – a placement that is four years away. However, the exposure to medicine I gained at MGH has already given me an idea of the specialties that I wish to pursue and so I am able to join interest groups and begin networking to advance my career. My research experiences have already opened up a few doors regarding interning at summer programs for medical students to supplement their resume with additional research projects. On a day to day basis, the skills I learned during my time at MGH have been extremely useful during medical school. My experience in an academic hospital has prepared me for the medical school environment as there is an interlacing of academic work and patient care during all hours. Furthermore, I find that some assignments are easier as I am used to rapidly acquiring and digesting scientific literature. However, I am most amused at how the little abilities that you acquire become surprisingly beneficial later in life. Attending the Hookerlab presentations has made me a Microsoft office pro and I've already been nominated as a tech whiz in my problem based learning group. Working at the Martinos Center has benefitted my medical education in more ways than I could have imagined.

Finally, I asked myself what it was like to work with Dr. Jacob Hooker and unexpectedly found myself more appreciative than I would have anticipated. He has helped several of my colleagues to achieve their goals of graduate school, medical school, and professional placement. It is apparent to everyone in the field that he is the rare type of primary investigator; a rising star in science that constantly publishes material, undertakes new studies, wins grants, and builds his research team. However, the following is my honest assessment of my boss for two years. Keep in mind that he is no longer paying me and so I am not obligated in any way to express any of the following. Simply put, Jacob is the only individual that I have ever met and considered to be truly gifted. On top of being renowned as a chemist, I have seen him show unrelenting enthusiasm and proficiency when working in all manner of endeavors including: engineering, mathematics, teaching, speaking, etc... and even athleticism (he has finished multiple Ironman competitions). Yet despite his talents, he is a humble, compassionate, and empathetic man. On numerous occasions, he took significant time from his day to listen to me vent personal matters, always offering me advice and encouragement. I have seen him do the same for several other employees and associates. I admire him professionally, respect him as a person, and I consider it an honor to work alongside him. That being said, good luck to all of the future lab members and associates. I hope you find your time with the Hooker group as rewarding and gratifying as I did.

Monday
Aug052013

Group Meeting Presentation Tips

First Group Meeting Presentation

 

Giving a presentation for the first time is always a bit nerve racking, especially when you’re new to a lab. Scientific presentations can be pretty different from those for other fields because even within a lab, knowledge about different subjects, instruments and techniques can vary greatly. This variation was one of the many things I tried to consider when I gave my first presentation in the Hooker Lab Group Meeting last week. Before I gave my presentation, I was able to have a subgroup meeting with Dr. Hooker and my fellow Summer Interns. After this meeting, I decided to compile a list of the things I found most important to include in my presentation, which could ideally (and hopefully) be helpful for any scientific presentation.

The tips are as follows (in no particular order):

1. Before you begin, think about the Big Picture of your project

             -What is the overall purpose?

                      +Is it linked to a particular disease, technology, etc?

2. What could/is the impact of this particular disease, technology, etc.

             -How many people are affected? What kind of symptoms do they experience? What is the current technology, medication, etc.?

3 Add visuals

             -Try to find pictures, illustrations, or data to supplement the text on your slides

4. When discussing drugs, instruments, proteins, etc. know general interesting facts about them

             -Mention them briefly during your talk

             -This could also be useful if people have questions

5. Include sources that are pertinent to your research

             -Papers with data, experimentals, etc. that influenced your project

6. When presenting values, provide context

             -Example: .4%proteins in the human body (is that big or small??)

                      +Rephrased: the substantial value of .4% of proteins in the human body…

7. When presenting data from instruments (ex. NMR, LC-MS) that may be unfamiliar to some people, give a bit of background on the machine

             -How does it work, what do certain peaks represent, what would ideal data look like

                      +Give structure for molecules used in experiment or photo of instrument or procedure 

                        for experiment

8. Are you telling a story?

             -Once you’ve completed a draft of your presentation, it’s always useful to look back at it and

              see if it flows (like a story)

                      +Try to think of yourself as someone outside of your field. If you looked at the slides

                         would you know what was going on? Would you be able to follow the presentation easily?

Hope this is helpful!

--Stephanie T.

 

 

Saturday
Jul202013

A New Use for FDG

Hello!

My name is Stephanie Threatt, and I am one of the four summer interns in the Hooker Group this summer. The projects of the summer interns span from computational data analysis of PET images to chemically synthesizing molecules to be used for PET imaging. I’m on the synthetic chemistry side, and lets just say, it can be a challenge.

The basis of my project is to utilize Fluorodeoxyglucose (FDG), which is a commonly used and synthesized radiolabeled molecule that resembles glucose, to eventually label proteins and amino acids. Labeling proteins is currently quite difficult because most radiochemical reactions require very harsh conditions, which would denature the proteins.

My mentor, Changning, and I have basically approached my project with two main steps.  1) Synthesizing fluoromalondialdehyde (FMDA) from FDG via an oxidation reaction and 2) Verifying the ability of FMDA to react and label an amino acid/protein.

I finally figured out the first step of my project a few weeks ago, and this was pretty exciting progress because the reaction method to form FMDA was not only fast but quite simple. I use periodic acid (H5IO6) to oxidize FDG into FMDA, with formic acid and formaldehyde as by products. For the reaction to go to completion, I simply mix FDG and periodic acid in water for 1 minute at room temperature.

Since we were able to confirm the synthesis of FMDA via NMR, we proceeded to the next step of my project. A commonly used research tool for reactions involving heavier, more complex molecules is called Liquid chromatography- Mass spectrometry (LCMS). Using the molecular weight of your product and it’s UV activity, you can determine if your product if being properly formed.

My mentor and I found that the excess periodic acid used to make FMDA was hindering the molecules ability to react with our chosen amino acid, arginine. Therefore, we tried various methods of quenching periodic acid, such as glycol, methanol and even glucose. After several reactions, which were analyzed using LCMS, we were able to determine that glucose successfully quenched periodic acid, rendering it unreactive so that the FMDA-arginine reaction could proceed. Additionally, the need for HCl needed to be evaluated because arginine will only react with FMDA if it is properly protonated.

Determining the appropriate conditions in which to synthesize FMDA and react FMDA with arginine in the presence of formic acid, formaldehyde and periodic acid was quite challenging, but yesterday I collected some very promising data using LCMS. Though I will need to confirm the results by repeating the experiment, I am very hopeful that I may have found good conditions to complete both steps of my project, and if so, I will move to using “hot” 18FDG, which will be really exciting.

I’ll be sure to keep the blog updated with my progress, and thanks for reading! Everyone in the Hooker Group does such fascinating research, so I urge you to keep reading!

 

-Stephanie T.

Saturday
Jul132013

A sweet adventure!

 

I guess everybody has a different story how he/she joins the Hooker group. Through my entire PhD, I was working on hard-core organic synthesis. Every day, I struggled to get better yield and ee for a new methodology and I really enjoyed it. When looking for a postdoc, I decided to apply for those groups where my chemistry skills would be expanded beyond just organic chemistry. 

Then I was introduced to Jacob and joined the Hooker group.   The past couple of months has been a really sweet adventure for me - radiochemistry, automation, radiotracer development......I was and am learning new things every day. The project is very exciting - it is really solving a problem, not just a publication (Nothing wrong with publications. I love to publish!). For the FIRST time, I see the translational power of chemistry. And for the first time, I see the practical use of my chemistry! The group is very diverse; we have experts on neuroscience, on radiochemistry, on PET imaging, of couse on organic synthesis :)-...... And group members are awesome!!!! The woking philosophy-efficiency matters the most-makes the working environment so pleasant! 

Hong :)-

 

Saturday
Jul132013

History of Neuroscience

If you have not come across the YouTube video series "History of Neuroscience" I encorouge you to take a look.  I just finished watching the video by Louis Sokoloff , which I highly recommend for anyone to watch who does FDG-PET imaging.  At some point, I will try and blog about how important the 2DG and later FDG methods have been for neuroscience.  For me, it was an honor to train with Joanna Fowler at Brookhaven National Lab (where FDG was invented) and such a delight to continue working with Joanna on projects in my current position.  I'm inspired by how one molecule developed by chemists can have such a profound influence on knowledge.  I was drawn to PET imaging as a chemist because of the translational power that PET provides a chemist for studying living human beings.  I'm proud to have a research group that is diverse but is rooted in chemistry.  I have the pleasure of working with and training incredible neuroscientists, biologists, biochemists, and chemists.  I hope that through blogging, our group will convey the types of research problems that we find exciting and what it is like to work with us.