Faces of LMP: Q&A with Professor George Charames
By Michelle Lee
It took 19 years of international research efforts to map out the entire human genome. Since the completion of the Human Genome Project in 2003, current technology can now sequence a person’s genome within a few days for much lower cost, providing new insights into the genetic causes of disease.
Genes contain instructions for cells to carry out essential functions, and errors in these instructions can result in a wide variety of diseases. The latest technology to analyze the gene, called next generation sequencing (NGS), has tremendously improved the accuracy and cost of disease diagnosis and treatment.
At the forefront of this cutting-edge diagnostic technology is George Charames, a professor in the Department of Laboratory Medicine and Pathobiology (LMP). Charames is also the Director of Molecular Diagnostics at Mount Sinai Hospital, where he earned both his Master’s and PhD under the supervision of LMP Professor Bharati Bapat. He completed a postdoctoral fellowship in clinical molecular genetics at Johns Hopkins University, and is board-certified by the American Board of Medical Genetics and Genomics.
In this Q&A, Charames explains how progress in DNA sequencing technology can help patients, and what the future holds for this quickly evolving field.
What exactly is molecular diagnostics? In molecular diagnostics we use genetic techniques in a clinical setting to help make diagnoses. We do this in many different ways. We look at how a person’s genes predispose them to certain diseases, or how genes affect their response to drugs. We work closely with the genetic counselors in the clinics to best determine how we can help patients.
What is life like as the Director of Molecular Diagnostics? Extremely busy. One defining technological change that has happened in the last few years is next generation sequencing, and adopting that in the clinical lab has significantly increased the workload of every lab director. There is potential to do much more with this instrumentation and technology, and everyone is trying to keep up with it. Usually, a lot research is done before we feel that a technique is ready for use in a clinical setting. But it feels like NGS is happening almost in parallel in both the research and diagnostic worlds. It’s pretty exciting and extremely hectic.
What are the highlights and lowlights of your job? Highlights are developing these new tests that we know will benefit patients far more than before, and working in a time when I know that, during my career, I will see drastic improvements in genetic tests in the field of molecular diagnostics. One of the lowlights is the fact that funding is drastically becoming the biggest hurdle, more so than creating new technology. But my success in difficult financial times is owed to the support of Dr. Rita Kandel, Chief of Pathology at Sinai. To advance our lab and keep pace with changes in this field, and in our provincial health-care system, you must have the support of the department. I am quite fortunate in this regard.
What are the latest technological developments in this area? The latest development is NGS. It’s being improved yearly. Previously, when you bought a sequencer, you would use it for a decade. Today, new and better sequencers are being produced every year. Chemistries are improved upon, and it’s increasing our sensitivity for detection. We used to sequence one fragment for one patient in one tube at one time, with a maximum of 96 wells. Now we can sequence for 24 to 96 patients in one tube and we can sequence 5,000 genes at a time for a number of patients in one instrument at one time. Of course, you wouldn’t do that for every patient, but having the room and technology to do so means we’re limited not by technology but by what ethically and clinically makes sense for the patient.
What is the future of molecular diagnostics? Whole exome sequencing on every patient is the future. This means sequencing all the coding regions of every gene in your body at low cost, but analyzing only the genes that are relevant to the disease at the time that you are presented with some kind of a clinical indication. Clinical exome sequencing is already performed and funded, but only for specific indications. Besides the cost of the test, there are barriers like the cost of storage and logistics of storing this information, but people are making it their life’s work to solve these issues.
How did your experiences at LMP prepare you for your postdoctoral fellowship and this position? It prepared me immensely. LMP has been very supportive of me since the beginning. For example, Dr. Sarma, Dr. Elsholtz, Dr. Gotlieb and Dr. Hegele were all extremely helpful. We have a very good department and it’s becoming internationally known. My research supervisor was Dr. Bharati Bapat, and I owe everything to her because she allowed me to keep my finger on the diagnostic side while I was still working on my research project. I had publications based on both basic research and clinical diagnostics, and this breadth made my application attractive when I was looking for postdoctoral fellowships and training sites. At Johns Hopkins, I was the only one accepted out of numerous applicants from all over the world. Had I not been able to experience the diagnostic side by working in a diagnostic environment, I don’t know if my application would have been much different than hundreds of others who applied to Hopkins.
What advice would you give to undergraduate and graduate students who are interested in pursuing a career in this area? Determine that this is what you want. Training sites for this type of postdoctoral fellowship don’t want students who just defaulted to clinical molecular diagnostics. They want students who wanted it and aimed for it from an early stage in their careers. To demonstrate this enthusiasm, I would advise showing that you’ve done a lot of translational and clinical research, and maybe even worked in a lab that offers a clinical service. It’s important to fully understand what a molecular director does and the difference between research and diagnostics. If you can understand that, then your application will be regarded favourably for these very competitive training programs. The resources are here — it’s what you do with them. I’d say a lot of what I achieved was based on luck and timing, but a major part of what you can control is using the resources you’ve got and planning out your route early on.