The work, recently published in the journal , reveals an underappreciated connection between genetics and our antibodies. Antibodies are key players in our immune system, with important roles in human health and disease, including in infection, autoimmunity, cancer and even vaccine responsiveness.

“Our work demonstrates that not everyone has the same capacity to generate certain types of antibodies due to genetics,” said Oscar Rodriguez, a post-doctoral fellow at UofL, and the first author of the study. “This could have critical implications for how we assess outcomes related to treatments and vaccines that depend on the antibody response.”

Vaccines, for example, work by simulating a viral infection and triggering an immune response — a sort of drill that teaches the body what a virus looks like and how to fight it. While it’s commonly known that individual response to vaccines can vary from person to person, this work shows more clearly than ever that these variations may depend on the antibody genes a person has inherited.

“For a long time, we’ve assumed vaccines could be designed using a one-size-fits-all approach,” said Melissa Smith, director of the , and lead author of the study. “This research shows that genetics predisposes us to qualitatively and quantitatively different antibody responses. If this information could be used to understand when individuals will or won’t respond to a given vaccine or treatment, that could be hugely impactful.”

The research also revealed that differences in our antibody responses could be linked to broader patterns of genetic diversity across human populations. This stresses the need to better characterize diversity in the genes that encode antibodies, and specifically increase the sampling of understudied populations. This is one of the driving forces behind research being conducted by this team.

Critical for advancing this effort is the recent acquisition of a by the Sequencing Technology Center. UofL is one of only a handful of��service providers in the country to offer access to this technology. Its use by this team could help improve our understanding of ancestry-specific immune gene-associated disease through the characterization of antibody genes in thousands of individuals worldwide, leading to improved and more equitable patient care.��

“We are currently building the most comprehensive catalogs of human antibody genetic variation from diverse genetic ancestries,” said Corey T. Watson, associate professor in the , and senior author of the study. “By studying a greater number of populations across the globe, we will be able to clarify the contribution genes make in positioning our immune systems to respond in a variety of disease contexts, and hopefully inform next-generation treatments.”

Fire, a professor of pathology and of genetics at Stanford University, is famous for his role in the discovery of ribonucleic acid (RNA) “interference.” That discovery earned a .

“The things that have driven this field are curiosity, fundamental investigation and thoughtful mentorship,” Fire said.

Much like DNA, RNA plays a critical role in genetics, specifically in how our genes are coded, decoded, regulated and expressed. Fire’s Nobel-winning work revealed that interference could cause some genes to be “silenced” and not expressed. ��

In his talk at UofL’s Clinical and Translational Research Building, Fire focused on his current research into RNA’s role in the cellular immunity that protects organisms from viruses and infection.

The UofL talk was part of the , funded by benefactor Austin and Mary Francis Bloch and the and hosted by the School of Medicine’s .

Dr. Ron Gregg, chair of the department, said bringing Nobel winners like Fire to UofL provides faculty, students and staff with an opportunity to learn about the process that gave rise to the award, and gain a historical perspective on significant scientific breakthroughs that could inspire their own.��

“Having the awardees also talk about their current research provides insight into cutting-edge research,” Gregg said. “Most importantly, our interactions with these individuals lets us discuss the important research being done at UofL with them.”

But, according to University of Louisville professor Mark Rothstein, those tests could also provide information for companies deciding, say, whether or not to issue you a mortgage or sell you life insurance.

“The information could include important risk factors,” said Rothstein, founding director of the Institute for Bioethics, Health Policy and Law at UofL. He recently wrote about its use in life insurance underwriting in .

While federal law says employers and health insurers can’t discriminate based on genetic information, Rothstein said that the law doesn’t extend to disability, long-term care, life, or other insurance products.

And of those, he said, “life insurance is the huge gorilla in the room.”

According to the , 10.5 million individual life insurance policies were purchased in 2017. For long-term care and disability insurance, Rothstein says the respective number of policies is much smaller, about 100,000 and 550,000 respectively.

As of 2017, millions of people — possibly 1 in every 25 Americans — have used at-home genetics tests, according to . And, as it stands, home tests aren’t in your medical record (unless you put them there), so insurers don’t have access to that information anyway.

Rothstein said insurers are increasingly concerned that individuals will have more genetic information than they do, so they want access to tests performed in health care settings and might even seek to perform their own testing.

But if they did and could use the results to determine coverage, Rothstein said, people scared of losing life insurance may stop seeking DNA testing that could identify increased genetic risks for some serious conditions, such as genetic-based cancers.

“We know that a lot of people are not getting genetic testing who would benefit from it,” he said. “And my concern is that we’re missing an opportunity to save lives because individuals are worried about the economic consequences of genetic tests, and we need to figure out a way to prevent that from happening.”

Listen to Rothstein’s full interview on .��

Sharp shared the 1993 Nobel Prize in Physiology or Medicine with Richard Roberts, PhD, for 1977 research that revealed the first indications of “discontinuous genes” in mammalian cells. The discovery fundamentally changed scientists’ understanding of gene structure.

Sharp is an institute professor at the Massachusetts Institute of Technology in the Department of Biology. His research centers on the molecular biology of gene expression relevant to cancer and the mechanisms of RNA splicing. The author of more than 400 publications, Sharp is a member of the Koch Institute for Integrative Cancer Research at MIT. He is an elected member of the National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences, the American Philosophical Society and the Royal Society, United Kingdom.

The Kentucky native earned his BA in chemistry and mathematics from Union College in Barbourville, Ky.

The lecture begins at noon, Thursday, May 25, at the Kosair Charities Clinical and Translational Research Building, room 101-102. The event, hosted by the Department of Biochemistry & Molecular Genetics of the UofL School of Medicine, is part of the Austin and Mary Frances Bloch Lecture Series, established in 1999 in honor of Austin Bloch and his wife, Mary Frances Bloch. Austin Bloch practiced medicine in Louisville for many years and served as an adjunct clinical instructor for the UofL School of Medicine.��

Sharp also will present a research seminar on Friday, May 26, in room 102 of the UofL School of Medicine instructional building on the topic, “Super-enhancer-associated microRNAs and phase transitions.”

Sharp is the second Nobel laureate to visit UofL this month. Peter Agre, MD, spoke on the Belknap Campus on May 8. Agre shared the Nobel Prize in Chemistry, 2003, with Roderick MacKinnon for his work in the discovery of water channels in cell membranes.��

Infertility can be devastating for those who long to have a child. Aside from the financial burden of infertility treatment, couples can face anxiety, depression and a variety of other health problems. Data from a Centers for Disease Control and Prevention U.S. National Health Statistics Report conducted from 2006-2010 found nearly 11 percent, or 6.7 million, of women ages 15 to 44 have an impaired ability to get pregnant or carry a baby to term and 6 percent, or 1.5 million, of married women ages 15��to��44 are infertile. ��

Kira Taylor, PhD, MS, assistant professor, Department of Epidemiology and Population Health in the UofL School of Public Health and Information Sciences, says exposure to tobacco smoke may be more harmful in women who carry the slow metabolizer form of NAT2, a gene that plays an important role in metabolism of toxins present in tobacco smoke and other hazardous substances.��

“We think that if a woman carries the slow form of the NAT2 gene, cigarette toxins will be metabolized and excreted more slowly, thus exacerbating the effects of smoking hazards – including making infertility problems more pronounced,” Taylor said.

Taylor and her research team will consider ovarian reserve – a woman’s remaining egg count – and in vitro fertilization success rates as they relate to the cumulative impact of smoking, exposure to secondhand smoke, and finally a combination of exposure to tobacco smoke and presence of the NAT2-slow gene.

Participants will provide a urine sample, which will be used to assess NAT2 genotype and recent exposure to cigarette smoke, and they will answer a questionnaire regarding lifetime exposure to cigarette smoke. Researchers will assess ovarian reserve through hormone levels and ultrasound, and success rates of in vitro fertilization procedures will be recorded.

“The results of this study will add to a growing body of evidence for the role of current smoking, past smoking and passive smoking on ovarian reserve and in vitro fertilization,” Taylor said. “We hope to determine for the first time whether the observed effects of smoking are stronger among women carrying the slow version of NAT2.”��

Study co-investigators include Henry Bohler, MD, associate professor, Department of Obstetrics, Gynecology and Women’s Health, and practicing physician with the University of Louisville Physicians Fertility Center; David Hein, PhD, professor and chair,��; and Rachel Neal, PhD, associate professor, Department of�� .

If Taylor and her colleagues find an interaction between NAT2 and smoking with regard to ovarian reserve or in vitro fertilization, it could pave the way for more accurate analyses of the effects of smoking. In addition, the NAT2-slow gene may be a biomarker for fertility specialists to consider as a predictor of in vitro fertilization success or failure. In the future, it also may be possible to treat individuals who are more genetically susceptible – those with the slow NAT2 gene – using personalized medicine in the form of drug or gene therapy to mitigate the effects of exposure to harmful substances.