Spring CTSI Seminar Series Previews “The New CTSI”

The CTSI Seminar series resumes for the spring 2016 semester on Tuesday, January 19th with a look at the “new CTSI.” The theme for the series is “The New CTSI: Connect, Learn, Get What You Need” and will feature presentations by the writing teams who collaborated on the recent Clinical and Translational Science Award (CTSA) application, which is intended to provide major funding for the CTSI’s next five-year cycle beginning July 2016.

CTSI Co-Directors

CTSI Co-Directors (left to right): Nancy Bennett, MD, Director of the Center for Community Health, Professor of Medicine; Martin Zand, MD, PhD, Professor, of Medicine; and Karl Kieburtz, MD, MPH, Senior Associate Dean, Clinical Research, Robert J. Joynt Professor in Neurology

The objective of the seminar series is two-fold:

  • To describe future plans for the CTSI as described in the 2015 renewal application
  • To inform the University community about resources offered by the CTSI

The mission of the University of Rochester Clinical and Translational Science Institute (UR-CTSI) is to develop, demonstrate and disseminate methods and approaches to advance translational research, by: 1) providing education and training, 2) fostering transdisciplinary teams, 3) improving quality and efficiency, and 4) engaging community and national stakeholders and partners. Our vision for the next five years is to become a replicable model environment for research, across the translational spectrum from molecules to populations, responsive to community priorities, conducted by transdisciplinary, patient- and community-engaged teams, that improves population health.

Co-Director Karl Kieburtz, MD, MPH, said “We look forward to sharing the evolution of the CTSA program on the national level and how we plan to respond to those changes, as well as the evolving needs of the Rochester research community, with our plans for the next 5 years”

The CTSI Seminar series is held on Tuesdays from 12:00-1:00 pm. The first session (January 19th) of the seminar series will be held in the Ryan Case Method Room (1-9576) in the Medical Center. The remaining sessions will be held in the Helen Wood Hall Auditorium (1w-304). All sessions will be streamed live. Lunch is provided; attendees should bring their own beverage. CME credit is also available for most sessions. The full schedule of seminar sessions is listed below and is also available here on the CTSI website. Also see the website for links to live streaming and archived recordings.

Date Speaker (s) Title
1/19/2016 Karl Kieburtz, MD, MPH; Martin Zand, MD, PhD; and Nancy Bennett, MD Overview of the CTSA Program
1/20/2016 E. Ray Dorsey, MD, MBA and Karen Rabinowitz, JD Telemedicine and Research

(Part of the Good Advice: CTSI Skill-Building Workshop Series)

1/26/2016 Office for Human Subjects Protection (OHSP) TBA
2/2/2016 Martin Zand, MD, PhD; Tom Fogg, MS; Ann Dozier, PhD; Sharyl Zaccaglino Administrative Core: Organization, Governance, Collaboration, Communication; Evaluation and Continuous Improvement; Quality and Efficiency
2/9/2016 Timothy Dye, PhD Informatics
2/16/2016 Nancy Bennett, MD; Gail Newton; and Katia Noyes, PhD, MPH Community and Collaboration: Community Engagement; Collaboration and Multi-Disciplinary Science
2/23/2016 Martin Zand, MD, PhD; James Dolan, MD; Edward Schwarz, PhD Translational Endeavors: Translational Workforce Development; Pilot and Translational Clinical Studies
3/1/2016 Karl Kieburtz, MD, MPH; Edwin van Wijngaarden, PhD; Rob Strawderman, ScD; Eric Rubinstein, JD, MPH Research Methods: Biostatistics, Epidemiology, and Research Design; Regulatory Knowledge and Support
3/8/2016 Office for Human Subjects Protection (OHSP) TBA
3/15/2016 Karl Kieburtz, MD, MPH; Karen Rabinowitz, JD; Carrie Dykes, PhD Network Capacity: Liaison to Trial Innovation Centers; Liaison to Recruitment Innovation Centers
3/22/2016 Nancy Bennett, MD; Steven Barnett, MD; Giovanni Schifitto, MD, MS Hub Research Capacity: Integrating Special Populations; Participant and Clinical Interactions
3/29/2016 Martin Zand, MD, PhD and Scott Steele, PhD Network Science / Regulatory Science
4/5/2016 Office for Human Subjects Protection (OHSP) TBA
4/12/2016 Timothy Dye, PhD and Robert Holloway, MD, MPH KL2 Career Development Program and TL1 Training Program
4/19/2016 CTSI Trainees CTSI Trainee Presentations
4/27/2016 Charles Duffy, MD, PhD and John Fahner-Vihtelic Cognivue: Assessing the aging brain – Patenting, Licensing, and Commercializing a Breakthrough Technology (Part of the Good Advice: CTSI Skill-Building Workshop Series)


CTSI Seminar Series hosts guest speaker from FDA

Carol Linden, Ph.D.

Carol Linden, Ph.D.

Carol D. Linden, Ph.D., Director of the Office of Regulatory Science and Innovation within the U.S. Food and Drug Administration (FDA) will present at the CTSI Seminar Series from noon to 1 p.m., Tuesday, Sept. 15, in Helen Wood Hall Auditorium.

Linden, who serves in the Office of the Chief Scientist, Office of the Commissioner, oversees a broad array of intramural and extramural programs that focus on bringing scientific and technological advances – and the education surrounding the regulation of these products – to the American public.

Her seminar will highlight some of the FDA’s initiatives to promote regulatory science, including through external partnerships. Largely, these partnerships focus on how the FDA can identify and integrate emerging scientific developments into the regulatory process to ultimately improve the development and approval of safe and effective medical products.

The lecture is part of the the Fall CTSI Seminar Series, which is themed “Advancing Regulatory Science and Translational Science: Research, Training and Partnerships.” Lunch will be served, but please bring your own beverage.

Director’s Update — February 2015

Every month, the CTSI Stories Blog will post excerpts from ongoing conversations with the institute’s co-directors.

Below, Nana Bennett discusses the spring CTSI Seminar Series on population health, and the CTSI’s emphasis on this field of growing importance.NanaBennett

Tell me a little about why this topic is so important.

The United States spends more money per capita on healthcare than any country in the world, and yet our health outcomes are very poor relative to most other developed nations. Overall, it’s evident that we, as a country, have not done well improving the health of our residents.

The CTSI is increasingly focused on health improvement and the ways in which research can contribute directly to population health improvement.  We initially described this approach as  pillar of the CTSI, but increasingly we are viewing it as an overarching goal.  Through the CTSI seminars, we hope to give everyone an introduction to population health, which is a way of thinking about how to increase the health of all of our citizens by addressing certain key issues. The US government has set a triple aim: to improve health, improve health care, and reduce cost, and in order to do that, it’s becoming more and more critical for both health care systems and health research to embrace a population health approach.

Why is there such a gap between what we spend and our outcomes?

There are a number of reasons. First, our system is set up to treat individuals, rather than populations. This means we spend a lot of money on new technologies and expensive treatments for individual problems, rather than allocating resources to prevention which will help the population’s health improve.

Additionally, it’s currently believed that the health care a person receives only accounts for about 10 percent of the health of that person. Behaviors, meanwhile, account for 40 percent. So we spend a lot of money treating the consequences of some widespread problems, such as obesity and tobacco-use, which could be more efficiently dealt with by addressing behaviors on the front end.

Those are a few examples from the clinical enterprise. On the research side, we’ve always focused on basic science discovery and exciting technologies. However, we have not ensured that our research dollars support studies that address the most important determinants of health and can be quickly translated into health improvement for the population as a whole.

With that as a backdrop, what is the CTSI doing to address population health?

The CTSI is formulating ways to place population health at its forefront. We want everything we touch — whether it’s our pilot grants, our education and career development, our research support programs — to somehow be moving towards the goal of improving the population’s health. We want to make translation into clinical and community solutions our primary goal. And, of course, this lecture series will introduce key concepts of population health and population research. We want to give everyone a grounding in this work in the hopes that they will consider this paradigm as they pursue their own interests.  We do not want to, in any way, diminish the importance of basic science, but rather hope to articulate the road to its translation into better health.


Previous director’s updates:

January 2015 – Harriet Kitzman reflects on her time as a CTSI co-director.
December 2014  – Karl Kieburtz offers his takeaways from the CTSI all-hands retreat.
November 2014 – Nana Bennett speaks to the expansion of the role of the CTSI’s Community Advisory Council.
October 2014 – Harriet Kitzman discusses the science of team science.
September 2014 – Karl Kieburtz talks about why the CTSI is beefing up its informatics team.
August 2014 – Nana Bennett discusses the new Population Health pillar.
July 2014 – Harriet Kitzman offers her takeaways from the Mini Summer Research Institute.
June 2014 – Karl Kieburtz gives an overview of the CTSI’s six pillars.

Seminar Recap: Sex Dependent Neurotoxicity of Ambient Ultrafine Particulate Matter

Between its contributions to heart disease, stroke, lower respiratory infections in children, and chronic obstructive pulmonary disease, air pollution plays a big role in our health. In fact, the World Health Organization believes that air pollution contributes to over 7 million premature deaths annually.

Joshua Allen, Ph.D.

Joshua Allen, Ph.D.

“So they’re really making this firm statement now that air pollution is the largest single environmental health risk,” said Joshua Allen, Ph.D., research assistant professor of environmental medicine.

But the health risks don’t end there, as there are now close to a dozen studies linking autism and schizophrenia to early air pollution exposure. Hoping to expand on these findings, Allen is now studying how the ultrafine particles (UFPs) that accompany air pollution into the lungs can affect the growing brain.

His work has shown significant differences between how these UFPs affects neonatal male and female mice. He shared his results at the CTSI Seminar Series on Women’s Health on Oct. 28.

UFP study

To administer his study, Allen collected air using a device that draws in 5,000 liters of air per minute, and  concentrating it 10- to 20-fold. The resulting enriched air contained approximately 200,000 UFPs per cubic centimeter, or about the same amount present in the air around an active expressway.

He then exposed neonatal mice to the UFP-enriched air, and used a variety of tests to measure their neurological development.

In one learning test, the mice were rewarded with food after pressing a sequence of levers. Normally-developing mice would improve their test accuracy over time, but that didn’t happen for the male mice exposed to the UFP-enrich air. During the test, if they pressed an incorrect lever, a light would turn off, shutting the reward system down temporarily.

“What’s really interesting in males is that they don’t stop responding,” said Allen. “The whole box shuts down, and for a normal animal, you would expect the response to then stop, because they would never be reinforced when the lights areoff. But the males didn’t stop. They just kept whaling away on the levers.”

This effect adversely impacted their ability to learn, and also had implications for impulsivity. Allen said that it wasn’t his intention to study how the exposures affected males and females differently, but rather that the data pushed him in that direction.

Conclusions and future directions

Ultimately, both males and females did show some neurological damage after exposure, but males were significantly more sensitive to the UFP-enrich air.

“We think the protection in females is probably related to differences in microglia colonization, and it might be a testosterone-mediated mechanism,” said Allen.

Allen is now following up on several other studies that have shown certain types of air pollution, such as diesel exhaust particles, can affect males and females differently. He’s also looking at early-life air pollution exposure in humans and looking at whether home location correlates with the onset of the autism.

“This was all very surprising to us,” said Allen. “We didn’t start out as experts in this type of thing, and we’re learning as we go, but given the links between autism and air pollution, we want to know more about this topic.”

Seminar recap: Unwanted pregnancy — A high-risk perinatal condition?

Obesity, diabetes, high blood pressure, tobacco use — there are a variety of reasons that a pregnancy can be classified as “high risk.”

But one factor that isn’t currently considered by most healthcare providers is whether the pregnancy itself is wanted to begin with, and data collected by the Perinatal Data System suggests that it’s something that healthcare providers may want to start taking into account.

Tim Dye, Ph.D.

Tim Dye, Ph.D.

Tim Dye, Ph.D., Professor in the Department of Obstetrics and Gynecology, and director of biomedical informatics at the CTSI, shared data from an analysis of the Perinatal Data System, which includes several hundred thousand pregnant women from the 22-county region of the Finger Lakes and Central New York. The seminar, which took place on Tuesday, Oct. 14, was part of the CTSI Seminar Series on Women’s Health.


Dye began studying the topic in the 90’s, when New York State began funding the Perinatal Data System. As part of the completion of a birth certificate, women were asked a standardized question “Thinking back to just before you were pregnant, how did you feel about becoming pregnant?” Based on responses from the approximately 300,000 live births that Dye and his team have currently sorted in the upstate New York registry:

  • 65 percent of live births were intended at conception, meaning the woman wanted to become pregnant when she did, or even sooner.
  • 28 percent had mistimed pregnancies, meaning they’d wanted to become pregnant, but not until later in life.
  • 7 percent were unwanted pregnancies, meaning they did not want to become pregnant at the time of conception, or at any point in the future.

The 7 percent of unwanted pregnancies represented approximately 20,000 women, giving a large enough sample size for Dye’s team to make some associations. After parsing the data, Dye found that the strongest statistical relationships to unwanted pregnancies were women who live in poverty, women with lower educational levels, and women at both extremes of the age spectrum (under 17, or over 40).

Women with pre-existing medical conditions, such as hypertension, diabetes, or other chronic illnesses, were also more likely to have an unwanted pregnancy.

“So it’s probably the women who are least likely to be able to financially deal with having an unwanted pregnancy who are the most likely to have one,” said Dye.

Additionally, women with unwanted pregnancies are also more likely to have maternal infections. They were also more likely to have a pre-term birth.


Many people assume that those with unwanted pregnancies are less likely to have or seek prenatal care, said Dye. But this isn’t actually true, as Dye’s statistics showed that 98 percent of women with unwanted pregnancies do have some amount of prenatal care.

This means that most women are encountering healthcare professionals at some point before they give birth. But despite the suggestive data about the various risks, women with unwanted pregnancies were actually no more likely to be referred for high-risk care than were other women.

“We certainly see that pregnancies unwanted at conception that result in a live birth are different from other pregnancies,” said Dye. “So it could well be a marker for pregnancy that might lead to different kinds of complications, exposures, and risks.”

For many factors, we don’t fully understand why this is the case yet, said Dye. But since it’s not a variable that is even assessed at intake all the time, unwanted pregnancies aren’t often dealt with clinically at this point.

Said Dye: “That may be something that providers should start thinking about.”

Seminar recap: Reproductive Issues in People with Epilepsy

For those with epilepsy, the impact of the condition stretches far into other parts of their lives, affecting, among other things, their reproductive health.

Men with epilepsy have decreased sperm counts, and their sperm have abnormal morphology and impaired motility, making it harder for them to father children. Women, meanwhile, have higher rates of menstrual disorders due to their endocrine dysfunction, the type of epilepsy that they have, and they tend to have higher rates of polycystic ovary syndrome, due in part to the effect of epilepsy medications.

Lynn Liu, M.D.

Lynn Liu, M.D.

On Oct. 7, Lynn Liu, M.D., associate professor of neurology, pediatrics, and anesthesia at URMC, spoke at the CTSI Seminar Series on Women’s Health, sharing her experience treating patients with epilepsy who are attempting to have children, and offering directions for future studies.

Variety of issues

Before discussing hormonal issues, Liu mentioned the myriad obstacles that patients with epilepsy face.

Due to their condition, people with epilepsy are often barred from driving. This makes it tougher to get a job, putting many of them in lower economic brackets. Often, they live with family members, who are able to take care of them if and when they have a seizure.

“But if they’re not working, they feel overprotected by their family who feel obliged to take care of them, and they become more and more isolated,” said Liu.

These factors combine to raise the likelihood of mental health issues, which are borne out both in practice, and in the statistics — at least 30 percent of people with epilepsy have a mood disorder or some sort. They are also 10 times as likely to take their own lives.

They’re also less likely to marry, and more likely to divorce, said Liu, though she cautioned that this can depend on their age of epilepsy onset.

Physiological differences also exist, due to the release of hormones that occurs during seizure. Estrogen and progesterone levels are altered, which can affect fertility. Prolactin, a necessary hormone for sexual gratification, is also released during seizure, causing many patients with epilepsy to not have enough when they are intimate.

Treatment and other areas of need

Even if women are able to become pregnant, they must deal with the worry that they could have a seizure and fall, injuring the developing child. Seizure during delivery is also a concern; Liu recommends that her pregnant patients be reassured that a Caesarean section could be possible.

In the meantime, there are a variety of medications available to pregnant women with epilepsy. The challenge for both physicians and their patients is to find the right balance of medication that controls the seizures and doesn’t harm the fetus. Seizures themselves can cause birth defects, so they need to be controlled as much as possible, but medications can have side effects.

For example, said Liu. “All women of childbearing age should be on folic acid anyway, but “many of our seizure medicines have anti-folic properties,” so women with epilepsy especially should take folic acid.”

Various studies are currently being done on how much folic acid is appropriate, Liu said that data isn’t yet available on the ideal amount.

And while there are a few treatments available for men with epilepsy who are experiencing sexual dysfunction, there hasn’t been much research done on what can be done for women.

Said Liu: “It’s a lot harder of a question and an area worthy of a lot of exploration, because we don’t have a tremendous amount of options for women who have sexual dysfunction and decreased gratification.”

Seminar Recap: Studies in Uterine Fibroids

Most tumors, when discovered, are dealt with quickly — through removal, chemotherapy, or otherwise.

But uterine fibroids, benign in all but the rarest of circumstances, present an opportunity for researchers.

Donna Baird, Ph.D.

Donna Baird, Ph.D.

“Usually, when you find a tumor, you want to take it out,” said Donna Baird, Ph.D., principal investigator, epidemiology, for the National Institute of Environmental Health Sciences. “Fibroids are one of the rare times when you can look at tumor growth and describe it.”

Baird, a guest lecturer at the CTSI Seminar Series on Women’s Health on Sept. 30, shared her research on uterine fibroids, outlining her current work and offering new directions for future studies.

What we know

Uterine fibroids are smooth muscle tissue tumors which grow in the uterus of a majority of women in the middle to late reproductive years. They are extraordinarily common — in the United States, 70 percent of white women and 80 percent of African American women develop uterine fibroids at some point — and most of them are asymptomatic, with many women never realizing that they have them.

But some fibroids do grow to the point where treatment is necessary. Historically, uterine fibroids have been the leading cause of hysterectomies in the United States.

“So it’s a major health problem,” said Baird.

There are a handful of established risk factors — women in their middle-to-late reproductive years are most likely to develop fibroids, African Americans are at higher risk than white Americans, and early age of menarche and nulliparity also increase risk. But since uterine fibroid development is so common, simply measuring incidence may not provide much information about preventing development of disabling symptoms that are treated with major medical procedures, said Baird.

So, in a recent study, Baird’s group instead decided to focus on fibroid growth, enrolling 116 pre-menopausal women with clinically-relevant fibroids and measuring fibroid growth via MRIs over the course of a year.

While there was a wide variety of fibroid growth and shrinkage during the study period, the fibroids in the majority of women grew only a small amount — an average of 9 percent every six months.

Baird also found in a later study that about a third of fibroids seen at the beginning of pregnancy actually disappeared by 4 months after birth, consistent with their hypothesis that parity is protective because tumor tissue will be cleared during the process of postpartum uterine remodeling.

Current study

Since the publication of the growth study, Baird has begun a new study which involves a cohort of 1,696 African American women aged 23-34 in the Detroit area. Her group is following the women for five years and screening with ultrasound every 20 months to identify new fibroids and follow growth of already existing fibroids. They are testing whether Vitamin D could be a preventative in terms of fibroid development.

“If it were found to be effective, it would be wonderful — it’s cheap and it’s easy,” said Baird. “Of course, we have lots of other questions. For example, there’s an interesting hypothesis that heavy bleeding actually causes fibroids.”

They’re also hoping to identify other potential factors that put certain women at higher risk for growing fibroids. Through prevention, Baird and others are hoping to make a dent in the more than $6 billion spent on this understudied women’s health condition each year.

Said Baird: “I think down the road, this is what can happen, and there can be much less surgical treatment and many fewer hysterectomies.”

Seminar Recap: Cognition in the Menopausal Transition

Labeled “The Seven Dwarves of Menopause,” they grinned out at the audience from the projector screen in Helen Wood Hall Auditorium: Itchy, Bitchy, Sweaty, Sleepy, Bloated, Forgetful, and Psycho.

“So, I’m interested in numbers 2, 6, 7, and a little bit of 4,” quipped Miriam Weber, Ph.D., assistant professor of neurology and obstetrics and gynecology, at URMC.

Miriam Weber, Ph.D.

Miriam Weber, Ph.D.

For the past decade, Weber has been studying cognition in women in the menopausal transition. While the symptoms embodied by the Seven Dwarves have long been accepted as common experiences for women in the menopausal transition, there hasn’t been a particularly robust array of science to support the cognitive symptoms until recently.

On Sept. 23 at the CTSI Seminar Series, Weber shared her past work in the field and discussed how her current study is expanding on her previous findings.

What we know

In creating her original study, Weber had a little background from two prior studies. The first, published in 2000 (SWMHS-Mitchell), found that 62 percent of middle-aged women reported an undesirable change in memory. Meanwhile, the longitudinal SWAN study had also found that 40 percent of peri- and post-menopausal women listed “forgetfulness” among a self-reported inventory of their symptoms.

With this data as a backdrop, Weber launched her Rochester Investigation of Cognition Across Menopause (RICAM) study, hoping to expand on the findings. The first study took place in 2005-2006, and a second took place from 2007-2009. Weber is now in the midst of her most comprehensive study yet, which began in 2010 and runs through 2015.

“Memory complaints really do reflect objective performance, maybe not in retentive memory, but in working memory,” said Weber.

Since publishing her initial results, other groups have reported similar findings — other researchers found that memory complaints were associated with loss of verbal memory and attention, that subjectively recorded memory problems were associated with objective measures, and that the brains of post-menopausal women with cognitive complaints were working harder in order to perform to previous levels.

“These are high-functioning women, and they’re not impaired, but they’re noticing subtle differences,” said Weber.

Weber’s study also looked which women were struggling the most with memory symptoms, and found that women in early post-menopause — the first year after the post-menstrual period — were performing worse with verbal learning, verbal memory, and fine motor and dexterity, than women in the late-reproductive stage.

Future directions

In confirming that women are indeed good at self-reporting their memory symptoms during the menopausal transition, Weber offered a few directions for future studies.

Among other suggestions, Weber said that researchers need better measures of symptoms known to impact cognition.

“With that in mind, we just received funding to add to RICAM objective measures of hot flashes and sleep monitors,” said Weber. “That way, we can get subjectively reported symptoms as well as objective measures.”

She’s also hoping to expand the study to multiple sites and make it more representative, which may allow for more parsing of the data.

“Ideally, we need to identify who is at risk for cognitive declines. Clearly, some women are doing better and some who are taking a more significant hit,” said Weber. “So I’m interested in describing in general what the experience is during this time period for all women, but also whether there are certain factors that put some women at increased risk.”

Seminar Recap: Environmental Exposures and Antinuclear Antibodies (ANAs)

When it comes to autoimmune diseases — conditions such as lupus, rheumatoid arthritis, and multiple sclerosis that cause a body to attack itself — women are at a higher risk than men.

But the reasons why aren’t completely clear.

Todd Jusko, Ph.D.

Todd Jusko, Ph.D.

Antinuclear antibodies (ANAs) are present in patients with autoimmune conditions, but the vast majority of ANAs haven’t been tied to certain diseases. Without good biomarkers to use when testing patients, diagnosis can be challenging, and prevention becomes nearly impossible.

So researchers at URMC are working to understand more. On Sept. 9, at the CTSI Seminar Series, Todd Jusko, Ph.D., assistant professor in the Department of Public Health Sciences and Department of Environmental Medicine, shared his past work and his search for an easy-to-identify biomarker.

What we know

Jusko was part of a group that looked at ANA prevalence in 4,340 individuals from the National Health and Nutrition Examination Survey, or NHANES between 1999 and 2003. Among those participants — 14 percent tested positive for ANAs in their blood. The proportion was slightly higher for African Americans, and, interestingly, slightly lower for individuals who were obese or overweight.

Women were also much more likely than men to test positive for ANA prevalence, particularly in their reproductive years, or just beyond. Overall, 18 percent of women tested positive for ANA, while 10 percent of men did. Women aged 30-39 were 2.5 times as likely to have ANAs in their blood as men. Women aged 40-49 were four times as likely. Nulliparous women — women who have not carried a pregnancy past 20 weeks — were also found to be much less likely to have ANAs present in their blood.

“Certainly, it’s related to some sort of hormonal difference,” said Jusko.


For a more recent study with the NHANES database, Jusko began searching for environmental causes of ANA. Dioxins and dioxin-like compounds have been documented to alter immune function, so it seemed logical that their presence may play a role in ANAs.

Jusko did find that one compound, triclosan, was biologically plausible as a potential cause of ANAs in men only, but his research revealed a variety of limitations with the data available. Jusko stressed the need for further studies measuring incident, or newly arising ANA and linking it to environmental chemicals.

“We were underpowered for some analyses. I know we had 4,300 people, which sounds like a lot, but some of the cycles didn’t measure the ANA or the chemical concentration,” he said. “So this was exploratory and this is far from the final word.”

Seminar Recap – When Erythrocyte Biology and Mechanics Collide

Right now, hundreds of thousands of units of blood are in storage in blood banks across the country.  But in terms of shelf life, they won’t last much longer than a gallon of orange juice.

Due to their short lifespan, the Red Cross requires for red blood cells to be used in 42 or fewer days after donation.  In addition to a steady need for new or returning donors — the Red Cross relies on 9.2 million donors each year — this leads to the staggering costs associated with hosting nearly-constant blood drives.

But in recent months, researchers at the University of Rochester have been working on a way to use embryonic stem cells to generate red blood cells for clinical use.

James Palis, M.D.

James Palis, M.D.

James Palis, M.D., professor of pediatrics, hematology, and oncology in the Medical Center, and Rick Waugh, Ph.D., chair of the biomedical engineering department on River Campus, shared their research at an April seminar in Helen Wood Hall auditorium.

Problems of scale

A study from France that was published in the journal Blood in 2011 showed that red blood cells grown outside the body could be successfully infused back into a patient, and had lifespans on par with those of normal red blood cells.

“So there is a proof of principal that you can start with a source of progenitors, expand red cells and use them as a potential source of transfusion therapy,” said Palis.

Palis wanted to see if he could use embryonic stem cells and erythroid progenitors to generate self-renewing erythroblasts.  After some successful preliminary results, Palis said that this type of red blood cell generation could be feasible on a larger scale.

However, each microliter (1/1,000,000th of a liter) of human blood contains 5 million red blood cells.  This means that the average person has about 25 trillion red blood cells in their body at any one time.


Richard Waugh, Ph.D.

“So if, ultimately, this is going to serve as a source of blood, our biggest problem is one of scale,” said Palis.  “Trying to synthesize that order of red cells is a mindboggling thought.”

Palis’s erythroblast cultures expand to a maximum concentration of about 2 million per 1 mL of media.  This means that his cultures would need about 1,000 liters of media to generate just a single unit of blood.

“Clearly, that’s a crazy thought, so we said ‘It’s time for a bioengineer to help us figure out if it’s possible to grow more cells with less (media),” said Palis.

Significant challenges

Waugh stepped in, and worked with a team to create several bioreactor models that could fulfill this function.

Early attempts produced a decent number of cells, but a great majority of those cells had died in the process.

“So as you can see, there are some significant challenges when you try to go from standard culture dishes to something that can be operated without daily involvement of the technician, and without having to put together 1,000 units of media to produce a unit of blood,” said Waugh.

But Waugh said that the team has had some success using a new bioreactor that they’d recently developed.  He didn’t give many details about it, saying that the team was planning to submit a patent on it, but one of Waugh’s students was able to use the bioreactor to grow red blood cells for three days, unattended, with 92 percent of the cells viable at the end of the process.

Waugh said that there is much work to be done, but he agreed with Palis that this method of red blood cell production could potentially be viable down the line.

“These self-renewing erythroblasts really show enormous promise for producing blood cells on a large scale,” said Waugh.  “But we’re going to have to improve our bioreactors significantly if we’re going to get to the place where we’ll have some practical application.”