Emory’s Max Cooper was celebrated this week in Nature for his discovery of B cells in the 1960s, while working with Robert Good at the University of Minnesota.
Cooper in Good’s laboratory in the 1960s (source: National Library of Medicine)
B cells are immune cells that display antibodies on their surfaces, and can become antibody-secreting plasma cells. Without B cells: no antibodies to protect us against bacteria and viruses. Where B cells come from, and how they can develop such a broad repertoire of antibody tools, was a major puzzle of 20th century immunology, which Cooper contributed to solving. (See the Nature piece to learn why the “B” comes from the name of an organ in chickens.)
The authors did not mention that Cooper is now at Emory studying lampreys’ immune systems, which are curiously different from those of mammals. The similarities and differences provide insights into the evolution of our immune systems. In addition, scientists here are exploring whether lamprey’s antibody-like molecules might be turned into anticancer drugs.
It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After diverting some of these topics into the 2015 crystal ball
, I corralled them into themes.
1. Cardiac cell therapy
2. Mobilizing the body’s own regenerative potential
4. Parkinson’s disease therapeutic strategies
(Gary Miller, better packaging for dopamine could avoid stress to neurons).
5. Personal genomics/exome sequencing
, like Emory’s Robert Gross
and Costas Hadjpanayis, do amazing things
7. Fun vs no fun
Our Web expert
tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
A new paper in PNAS from geneticist Steve Warren and colleagues illustrates the complexity of the protein disrupted in fragile X syndrome. It touches on how proposed drug therapies that address one aspect of fragile X syndrome may not be able to compensate for all of them. [For a human side of this story, read/listen to this recent NPR piece from Jon Hamilton.]
Fragile X syndrome is the most common single-gene disorder responsible for intellectual disability. Most patients with fragile X syndrome inherit it because a repetitive stretch of DNA, which is outside the protein-coding portion of the fragile X gene, is larger than usual. The expanded number of CGG repeats silences the entire gene.
However, simple point mutations affecting the fragile X protein are possible in humans as well. In the PNAS paper, Warren’s team describes what happens with a particularly revealing mutation, which allowed researchers to dissect fragile X protein’s multifaceted functions. Read more
Alzheimer’s protein pathology
While a wise Dane once proposed that predictions are dangerous, especially concerning the future, it’s usually helpful to plan ahead. Here are five biomedical research topics we think will occupy our attention in 2015.
1. Alzheimer’s We’re hearing discordant music coming from Alzheimer’s researchers. Large pharmaceutical companies are shutting down clinical trials in frustration, but researchers keep coming forward with biomarkers that might predict future disease. This confusing situation calls for some new thinking. Allan Levey, Jim Lah and colleagues have been preparing the way for a “beyond the usual suspects” look at Alzheimer’s disease. We are looking forward to Levey’s appearance at the 2015 AAAS meeting and to drug discovery wizard Keqiang Ye’s continuing work on new therapeutic targets.
2. Ebola While the scare over Ebola in the United States may be over (we hope so!), the outbreak continues to devastate countries in West Africa. Clinical trials testing vaccines and experimental drugs are underway or will be soon. Read more
Please welcome stem cell/cardiology researcher Hee Cheol Cho to Emory. Starting in September, Cho joined the Wallace H Counter Department of Biomedical Engineering at Georgia Tech and Emory, and Emory-Children’s Pediatric Research Center. He and his team will focus on developing gene-and cell-based therapies for cardiac arrhythmias. Their research will adding to and complement the research of several groups, such as those led by Chunhui Xu, Young-sup Yoon, Mike Davis and W. Robert Taylor.
Cho comes from Cedars-Sinai Medical Center in Los Angeles, where he specialized in understanding cardiac pacemaker cells, a small group of muscle cells in the sinoatrial node of the heart that initiate cardiac contraction. These cells have specialized electrophysiological properties, and much has been learned in the last few years about the genes that control their development.
Cho and colleagues from Cedars-Sinai recently published a paper in Stem Cell Reports describing how the gene SHOX2 can nudge embryonic stem cells into becoming cardiac pacemaker cells. Read more
Researchers at Emory have been revealing several connections between cells’ responses to starvation and immunological memory. The latest example of this is a paper in Nature Immunology from Rafi Ahmed’s lab, showing that the cellular process of autophagy (literally: self-consumption) is essential for forming and maintaining memory T cells.
This finding has some practical implications for vaccination and could point the way to additives that could boost vaccine effectiveness in elderly humans. Researchers at Oxford have demonstrated that autophagy is diminished in T cells from aged mice, and T cell responses could be boosted in older mice using the autophagy-inducing compound spermidine. Read more
Much of neuroscientist Shannon Gourley’s work focuses on the idea that adolescence is a vulnerable time for the developing brain. She and graduate student Lauren DePoy recently published a paper in Frontiers in Pharmacology showing that in adolescent rodents, cocaine exposure can cause the loss of dendritic arbors in part of the brain important for decision-making.
The researchers examined neurons in the orbitofrontal cortex, a region of the brain thought to be important for “linking reward to hedonic experience.” It was known that stimulants such as cocaine can cause the loss of dendritic spines: small protrusions that are critical for communication and interaction between neurons.
“To make an analogy, it’s like a tree losing some of its leaves,” Gourley writes. “Lauren’s work shows for the first time that if cocaine is given in adolescence, it can cause the loss of dendrite arbors – as if entire branches are being cut from the tree.”
The mice are exposed to cocaine over the course of five days in early adolescence, and then their behavior is studied in adulthood. This level of cocaine exposure leads to impairments in instrumental task reversal, a test where mice need to change their habits (which chamber they poke their noses into) to continue receiving food pellets.
The findings suggest a partial explanation for the increased risk of dependence in people who start using cocaine during adolescence.
One of Lab Land’s regular features is a post exploring a biomedical term that seems to be appearing frequently in connection with Emory research. This month I’d like to focus on frailty, which has been an important concept in treating elderly patients for some time. (This piece in The Atlantic nudged me into it.) Assessing frailty is emerging as a way for surgeons to predict post-operative complications.
Several teams of researchers have been trying to develop a standardized way of measuring frailty to aid in weighing the risks and benefits of surgery. Frailty may seem like a subjective quality (echoing Supreme Court Justice Potter Stewart’s remarks on obscenity: “I know it when I see it”) but if frailty can be defined objectively, doctors and patients can use it to help in decision-making.
Frailty can be thought of as a decrease in physiological reserve or a decrease in the ability to recover from an infection or injury. Much of the credit for developing the concept of frailty should go to Linda Fried, now dean of Columbia’s school of public health. While at Johns Hopkins, her team developed the Hopkins Frailty Score: a composite based on recent weight loss, self-reported exhaustion, low daily activity levels, low grip strength and slow gait. Read more