May 6, 2016

Walker brings Molecular Genetics Expertise to the Myeloma Institute

Brian WalkerAspecialist in molecular immunology and molecular genetics, Brian Walker, Ph.D., left his native United Kingdom (UK) in October 2015 to join the Myeloma Center as professor of medicine and director of research.

As a high school student in Scotland, Walker expected he would pursue a career in mathematics until “a good biology teacher changed all that.” 

Following his newfound passion, he studied general biology for two years and then specialized in medical microbiology at the University of Edinburgh.

For Walker, the appeal of medical microbiology “was the combination of immunology and disease, the host response to infection.”

Walker earned a Ph.D. in molecular immunology from Imperial College at the University of London in 2000 and then took a post-doctoral fellowship in molecular genetics at the Institute for Animal Health, now the Pirbright Institute, in the UK.

“I started my career studying the immune system of chickens,” he said.

The focus was on antigen processing as related to the recognition of foreign materials. Basically, a viral protein, or antigen, is chewed up inside the cell and put onto the surface of the cell in order for the immune system to be able to recognize the infected cell and stimulate an immune response to fight off the viral disease. Chickens are particularly good models for this type of study because they have a simpler immune system.

Some strains of chickens afflicted with the virus fight it off and do just fine, while other strains develop cancerous tumors and die. Genetics clearly plays a role. So, the challenge is to understand the molecular genetics and manipulate the system so that the appropriate response is stimulated to attack the cells that are infected.

In 2004, Walker’s interest was piqued by another postdoctoral fellowship opportunity, this time under Gareth Morgan, M.D., Ph.D., now the director of the Myeloma Center, who at the time was conducting cutting-edge research on novel microarray analysis at the UK’s Institute of Cancer Research (ICR).

Morgan was analyzing gene expression from myeloma patients with the goal of sub-classifying myeloma according to chromosomal differences. He was correlating the DNA changes with already established RNA classifications in order to identify the most important genes in terms of disease activity. Investigation of B-cell receptor mechanisms (myeloma is a malignancy of plasma cells, which are B-cells) is a continuing theme for Walker, as B-cells were first discovered in chickens.

Studies were conducted on 30-40 samples from newly-diagnosed patients across the UK
as part of a clinical trial at the ICR.  Utilizing DNA versus RNA for these studies had  γ

a distinct advantage. Because DNA degrades more slowly than RNA, the lag time from securing a sample to shipping it to the ICR to processing it did not compromise its integrity.

The studies, with Walker as lead scientist, enabled examination of the prognostic importance of molecular abnormalities in myeloma. Detection of poor prognostic markers helps identify high-risk patients who require more intensive treatment.

Much of the data on myeloma genetics is based at the chromosomal level. Walker’s team at the ICR performed whole exome sequencing, a technique for sequencing all the protein-coding genes in a genome (full set of chromosomes) on several large datasets. This enabled them to correlate abnormalities with the identification of prognostically important mutations and investigate the subclonal structure of myeloma at the mutational level. The information revealed that smoldering myeloma is very similar to myeloma, while MGUS (monoclonal gammopathy of undermined significance) is a less complex disease state. An understanding of the subclonal structure of myeloma is key
to understanding and predicting the efficacy
of treatments.

During his 10 years at the ICR, Walker developed high-level expertise in deciphering and understanding the role of molecular genetics in myeloma survival.

Following Morgan’s departure from the ICR to assume leadership of the Myeloma Center in July 2014, Walker moved on to the Royal Marsden Hospital in London to work on next generation sequencing for solid tumors, such as gastrointestinal and breast tumors.  (Next generation sequencing, also known as high-throughput sequencing, refers to a number of different sequencing technologies that allow scientists to sequence DNA and RNA more quickly than older methods, and, as such, have revolutionized the study of genomics and molecular biology.) But, he missed the myeloma work and was eager to join a high-volume, cutting-edge program.

Walker’s vision for future research directions at the Myeloma Center includes integrating gene expression profiling with DNA molecular profiling as a means of developing personalized treatments. This will ensure that patients receive the most effective therapy aimed at their unique disease features.

Walker looks forward to securing sophisticated equipment, specifically a NextSeq machine, to support this integrated profiling approach. The NextSeq can process targeted panels (versus the whole exome) with a very quick turnaround, ensuring that patients are placed on appropriate clinical trials and receive the most appropriate treatment as quickly as possible.  Additionally, the machine will enable creation of a pipeline for automated analysis. As soon as funding for the machine is secured, Walker and his team will be charting a new course for individualized medicine for myeloma patients.

Without missing a beat, Walker has adapted quickly to his new workplace and is actively advancing the research excellence for which the Myeloma Center is known worldwide.

As far as adapting to life in the United States, and particularly in a rural southern state, Walker is also making strides.

“I have already tried Gus’ Fried Chicken, and I like it,” he said.  “But I do miss the Cadbury Chocolate and Heinz Baked Beans that we get in the UK.”