The start of 2018 also marked my 15-year anniversary at UAB, having begun my tenure as Chairman of the Department of Genetics and Director of the UAB NF Program on January 2nd, 2003. At that time, the Department of Genetics consisted of only two full-time faculty members, subsequently merging with another department and increasing to 15 faculty. Today, the UAB Department of Genetics has grown to include 35 distinguished faculty members who continue to make significant contributions in clinical care, education, and research. Our program has also grown in scope over the past 15 years, with expanded patient care and initiatives in research and education. As part of a reorganization into adult and pediatric clinics, NF patients are now served at two distinct locations, including Children’s of Alabama and The Kirklin Clinic.  The NF Clinical Trials Consortium, for which UAB serves as the National Coordinating Center, is now in its third five-year funding cycle and is actively engaged in developing multiple new clinical trials for all forms of NF. In addition, our program has successfully secured NIH grants in genomic medicine focused on integrating genomics into diagnostic and therapeutic decision-making.  The department has three clinical laboratories, one of which – the Medical Genomics Laboratory – performs the most scientifically reliable and highest volume of NF genetic testing in the world. We also have an ongoing commitment to patient education through our annual support of key events such as the NF Symposium, NF Walk, and Rare Disease Genomics Symposium.

New Role as Chief Genomics Officer and Continued Role as Director of NF Program

Along with the significant growth our program has experienced over the past 15 years, the field of genomic medicine has continued to evolve since the completion of the Human Genome Project in 2003 that successfully sequenced the complete human genome. Since that time, our understanding of the role of genes in health and disease has greatly expanded, leading to the rapid growth of genomic medicine to provide individualized clinical care to patients. Genomic medicine uses an individual’s genetic profile to guide decisions about  prevention, diagnosis, and treatment.  UAB Medicine has committed to advancing research into genomic medicine through two initiatives aimed at collecting health data from participants to determine the impact of lifestyle, environment, and genomic profiles on a variety of health conditions.  UAB has launched the Alabama Genomic Health Initiative (https://www.uabmedicine.org/aghi) in collaboration with HudsonAlpha Institute for Biotechnology. We have been actively involved in recruiting participants in support of this initiative’s goal to enroll 10,000 individuals in our state over the next five years to determine how genomic information correlates with health status and risk of disease.  We are also the hub of a regional network as part of the NIH All of Us research program (https://allofus.nih.gov), which ultimately will recruit 1 million volunteers across the country.  Local enrollment in this program will begin soon.

In support of UAB Medicine’s commitment to implement precision medicine across all clinical programs, I have recently been appointed to the new role of Chief Genomics Officer for UAB Medicine, with the responsibility for establishing clinical programs in genomic medicine across the UAB Health System. This role also involves providing training and education to clinicians in the use of clinical tools to enable the use of genomic information in making diagnosis and treatment decisions. Because of this new role, I’ve stepped away from my position as Chairman of the Department of Genetics, as relinquishing the administrative responsibilities involved in that position will allow more time for me to focus on these new initiatives. I’ll continue to serve as a professor in the Department of Genetics and will also continue in concurrent positions as Associate Director for Rare Diseases in the UAB Hugh Kaul Precision Medicine Institute and as Co-Director of the UAB-Hudson/Alpha Center for Genomic Medicine.  From the perspective of the NF Program, nothing changes, as I’ll continue to direct the program, with ongoing involvement in clinical trials and research initiatives in developing genomic therapies. Also, I will continue to see patients in the NF Clinic with a continued commitment to maintaining the highest standards of clinical care.

2018 NF Symposium/NF Family Day Coming in April

The annual UAB NF Symposium, also known as NF Family Day, is scheduled for Saturday, April 7th, in the Bradley Lecture Center of the Children’s Harbor Building. This year’s keynote speaker will be New York University neuro-oncologist Kaleb Yohay, M.D., who will give a presentation about the role of alternative medicine in the treatment of NF. This annual event serves as a forum for NF patients and families to hear a series of presentations about a range of NF-related topics from clinical experts and also provides a means for establishing connections with other NF families. Event registration information is coming soon; for more information, please contact Ashley Cannon at ashleycannon@uabmc.edu  or Renie Moss and rpmoss@uab.edu

Newly Identified NF Mutation/Phenotype Correlation

Previously, I’ve discussed the ongoing efforts of the UAB Medical Genomics Laboratory to determine correlations between physical manifestations of NF (phenotype) and specific mutations in the NF1 gene (genotype). More than 3,000 mutations have been identified in the NF1 gene, and there are a few examples in which a specific mutation can be correlated to certain NF symptoms.  The January issue of the American Journal of Human Genetics (Am J Hum Genet. 2018 Jan 4;102(1):69-87. doi: 10.1016/j.ajhg.2017.12.001. Epub 2017 Dec 28.) features a paper from the UAB group and multiple collaborators, led by Dr. Ludwine Messiaen, that identifies a cluster of mutations in the NF1 gene that are associated with a relatively severe set of NF complications. This represents an example of a correlation between specific mutations and certain manifestations of NF.  It is known that most NF mutations turn off the gene, thereby destroying its function; there is no particular phenotype associated with these mutations, except the typical features of NF.   However, there are a handful of mutations where there is some ability to predict the phenotype. Identifying a correlation between a mutation and phenotype can be clinically valuable because certain complications can be anticipated with the potential of managing the condition more effectively. Also, a correlation provides information about how the gene works and may lead to answers regarding why some mutations result in a large burden of internal tumors but not many cutaneous neurofibromas, such as the mutations described in the recently published paper. With more than 3,000 NF gene mutations representing the largest repository in the world, the UAB Medical Genomics Laboratory, directed by Ludwine Messiaen, Ph.D., is in the best position for determining additional mutation/phenotype correlations. In 2016, using the repository of mutations and a catalogue of phenotypes (symptoms) in NF1 patients, Dr. Messiaen and her colleagues identified only the third genotype/phenotype correlation so far found for NF1. Some of these newly identified mutations are being reproduced in animal models, such as mice, rats and pigs, to observe the manifestations of NF correlated with these mutations. Also, we are developing a cell culture system that will help us to determine the way specific mutations alter function within the cell.   These studies will help us to classify the ability of specific mutations to cause NF1, and also will provide a system to test new approaches to treatment.