Message about my personal Vision:
While I have worked in academics and currently work at Merck, I always remember that the patient is my ultimate stakeholder. Everything I do in my professional career is to make the lives of patients better. I start with the simple yet profound questions that patients used to ask me when I practiced clinical medicine: “Why did I develop this disease?” “Will I respond to this medication?” “What is my prognosis?” “Will I ever be cured?“.
To answer these questions, I have been involved in a number of projects that deploy cutting-edge genomic technologies such as whole genome DNA sequencing and high-throughput cellular profiling in fresh patient samples; that link genomic measurements to detailed clinical data collected through electronic medical records (EMR), epidemiological surveys, social media networks, and smart phone “apps”; and that utilize bioinformatic analyses and computational modeling of genomic data to decipher biological networks in health and disease. In every experiment, large or small, I ask: How will this help discover new therapies to treat disease or new diagnostic tests to predict outcomes? For that is my ultimate goal: develop drugs and biomarkers to treat and diagnose patients. In this way, my discovery genetic and genomics research comes “full cycle” back to the patient. As new discoveries are made, the process is iterated, and the cycle spins onward towards better health.
In my current role at Merck, I use human genetic and genomic tools to test therapeutic hypotheses to advance drug discovery programs. The premise is based on what I think is the fundamental challenge facing the drug discovery ecosystem today: more than 90% of the compounds that enter clinical trials fail to demonstrate sufficient safety and efficacy to gain regulatory approval. Most of this failure is due to the limited predictive value of preclinical models of disease, and our continued ignorance regarding the consequences of perturbing specific targets over long periods of time in humans. It is increasingly possible to study humans to identify new drug targets, as well as make critical decisions at each stage of a drug development program.
There are three key ways in which our Department of Genetics & Pharmacogenomics (GpGx) uses human genetic and genomic data to advance MRL’s pipeline: (1) We use human “experiments of nature” — naturally occurring mutations in humans that affect the activity of a particular protein target or targets — to estimate the probable efficacy and toxicity of a drug targeting such proteins, as well as to establish causal rather than reactive relationships between targets and outcomes. (2) We use sophisticated genomic technology — for example, whole genome DNA, RNA transcriptional profiling, T cell receptor repertoire sequencing — to understand mechanism of action and to uncover new diagnostic biomarkers for therapies such as those that target the immune system in cancer. (3) We deploy cutting-edge genotyping and sequencing tools to make pharmacogenetic discoveries routine in clinical trials. [ To learn more about our GpGx Department, please see here. ]
My PlengeGen webpage and social media posts (@rplenge) represents a way for me to communicate ideas related to these themes. All ideas expressed here are my own. Please join me in this conversation, as together, we can help improve the lives of patients with a variety of diseases.
Robert Plenge (September 2014)