Pediatric Research Newsletter
Collaboration in Pediatrics and Environmental Medicine Improves Understanding of Developmental Lung Immunology
By Meghan Plog
Michael A. O'Reilly, Ph.D.
Michael O'Reilly, Ph.D., Professor of Pediatrics, is a developmental lung biologist who is interested in understanding how oxygen therapy given to preterm babies affects lung function later in life. Paige Lawrence, Ph.D., Professor of Environmental Medicine, is an immunologist and toxicologist who studies how environmental factors have positive and negative effects on immune system development and function. Their mutual interest in the developmental origins of lung disease led Drs. O'Reilly and Lawrence to establish a fruitful research partnership.
Initially, these investigators collaborated on a study that used a model system in which mice were exposed to increased levels of oxygen at birth. Once the mice reached adulthood, they were infected with influenza virus. Interestingly, the oxygen-exposed mice developed significant interstitial lung disease. In contrast, injection of the virus into non-lung tissues led to a normal immune response and no interstitial lung disease. They concluded that early life oxygen exposure affects the programming of the lung and its ability to mount a normal immune response to infection.
B. Paige Lawrence, Ph.D
To continue to explore these provocative findings, they recently submitted a grant application to study the expansion of a population of cells in the lung that may be responsible for the disrupted host response to respiratory viral infections. The long-term goal for the project is to identify a target that could be amenable to drug development. This work also involves collaboration with Luis Martinez-Sobrido, Ph.D., Associate Professor of Microbiology and Immunology. In addition, Drs. Lawrence and O'Reilly plan to collaborate on studies of the aryl hydrocarbon receptor, a protein that binds hundreds of environmental factors and has an extremely important role in the immune system. Recently obtained data suggest that it also has an important role in the lung. Importantly, the role of the aryl hydrocarbon receptor in the lung has not been extensively investigated.
When discussing their successful collaboration, both noted the importance of overlapping interests, but also differing perspectives. "We have a different toolbox, but it's not so different that we don't understand each other's toolboxes," said Lawrence. O’Reilly added, "She's not asking me to come out of my area of interest and I'm not asking her to come out of hers; so, it's the perfect Venn diagram." This decade-long collaboration has resulted in many publications, funding, and advances in research. O’Reilly and Lawrence are looking forward to continuing their work together with the goal of making additional contributions to our understanding of how fetal and childhood exposures affect lung immune function later in life.
Learn more about the work of the O'Reilly and Lawrence labs.
Yee M, Gelein R, Mariani TJ, Lawrence BP, O'Reilly MA. "The Oxygen Environment at Birth Specifies the Population of Alveolar Epithelial Stem Cells in the Adult Lung." Stem Cells. 2016 May; 34(5):1396-406. Epub 2016 Mar 07.
Pediatrics and Electrical and Computer Engineering Collaboration Wins University Research Award
By Meghan Plog
George J. Schwartz, M.D
George J. Schwartz, M.D., Professor of Pediatrics and Chief of the Division Pediatric Nephrology, in collaboration with Marvin Doyley, Ph.D., Associate Professor of Electrical and Computer Engineering, and Jeffery Purkerson, Ph.D., Research Assistant Professor of Pediatrics, recently received a University Research Award for their work on early detection of chronic kidney disease. This was one of eight projects to receive this prestigious award given each year by the University President. The group will be carrying out innovative experiments that use novel techniques in ultrasound to better understand the pathophysiology of acidosis and how it may cause the kidney to become damaged. Ultimately, the goal is to determine whether treatment with sodium bicarbonate could reduce or, possibly, reverse this damage.
Dr. Schwartz has spent much of his career micro-dissecting the collecting duct of the kidney using a model of metabolic acidosis developed over 30 years ago. As part of these studies designed to understand how the kidney adapts to metabolic acidosis, he observed that tissue extraction from acid-treated rabbits is more difficult than from normal rabbits. This observation indicated that the stiffness of the acid-treated tissue differed from normal tissue. Despite a very brief acid loading period (3-4 days), the animals develop significant acidosis. Irreversible fibrosis or scarring of the kidney from inflammation would not occur this quickly. However, this model will allow Dr. Schwartz to test their hypothesis that even short-term acidosis can cause kidney damage. In collaboration with Dr. Doyley, a novel ultrasound technology, used previously in oncologic studies, will allow the team to compare stiffness and elasticity of the acid-treated kidney tissue to that of untreated, normal kidney tissue.
If metabolic acidosis leads to changes in kidney stiffness, then the next step will be to determine whether the stiffness can be reduced or reversed by sodium bicarbonate treatment. Previous studies have shown that sodium bicarbonate treatment is effective in slowing the progression of kidney failure in patients with persistent metabolic acidosis. If the hypothesis proves to be correct, then it would support a more aggressive approach to the treatment of metabolic acidosis in the early stages of chronic kidney disease. Consequently, the team’s work has the potential to change the way pediatric and adult nephrology is practiced. Most importantly, this approach could slow the progression of kidney disease and potentially delay the need to initiate dialysis by many years.
Research Publication Highlights
2016 - 2nd Quarter
Association of blood pressure variability and neurocognition in children with chronic kidney disease. Lande MB, Mendley SR, Matheson MB, Shinnar S, Gerson AC, Samuels JA, Warady BA, Furth SL, Hooper SR. Pediatr Nephrol. 2016 Jun 5. [Epub] PMID: 27263021 [PubMed]
CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells. Steiner LA, Schulz V, Makismova Y, Lezon-Geyda K, Gallagher PG. PLoS One. 2016 May 24;11(5):e0155378. doi: 10.1371/ journal.pone. 0155378. eCollection 2016. PMID: 27219007
The Gluten-Free/Casein-Free Diet: A Double-Blind Challenge Trial in Children with Autism. Hyman SL, Stewart PA, Foley J, Cain U, Peck R, Morris DD, Wang H, Smith T. J Autism Dev Disord. 2016 Jan;46(1):205-20. doi: 10.1007/ s10803-015-2564-9.PMID: 26343026 [PubMed]
Protein arginine methyltransferase 1 is a novel regulator of MYCN in neuroblastoma. Eberhardt A, Hansen JN, Koster J, Lotta LT Jr, Wang S, Livingstone E, Qian K, Valentijn LJ, Zheng YG, Schor NF, Li X. Oncotarget. 2016 Aug 23. doi: 10.18632/ oncotarget.11556. [Epub] PMID: 27571165 [PubMed]
Feasibility of Early Palliative Care Consultation for Children With High-Risk Malignancies. Mahmood LA, Casey D, Dolan JG, Dozier AM, Korones DN. Pediatr Blood Cancer. 2016 May 3. doi: 10.1002/pbc.26024. [Epub] PMID: 27148856
An Essential Role for Pediatricians: Becoming Child Poverty Change Agents for a Lifetime. Plax K, Donnelly J, Federico SG, Brock L, Kaczorowski JM. Acad Pediatr. 2016 Apr; 16(3 Suppl):S147-54. doi: 10.1016/ j.acap.2016.01.009. PMID: 27044693 [PubMed]
Caregiver education to promote appropriate use of preventive asthma medications: what is happening in primary care? Frey SM, Fagnano M, Halterman JS. J Asthma. 2016;53(2):213-9. doi: 10.3109/02770903. 2015.1075549. Epub 2015 Aug 18. PMID: 26288255
Outcomes Using a Conservative Versus Liberal Red Blood Cell Transfusion Strategy in Infants Requiring Cardiac Operation. Cholette JM, Swartz MF, Rubenstein J, Henrichs KF, Wang H, Powers KS, Daugherty LE, Alfieris GM, Gensini F, Blumberg N. Ann Thorac Surg. 2016 Aug 2. pii: S0003-4975(16)30544-6. doi: 10.1016/ j.athoracsur. 2016.05.049. [Epub] PMID: 27496630 [PubMed]
Developmental Screening of Refugees: A Qualitative Study. Kroening AL, Moore JA, Welch TR, Halterman JS, Hyman SL. Pediatrics. 2016 Sep; 138(3). pii: e20160234. doi: 10.1542/ peds.2016-0234. Epub 2016 Aug 15. PMID: 27527798 [PubMed]