Pamela J. Kling, MD
Associate Professor
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Pamela Kling
6C Meriter-Park
202 S Park Street
Madison, WI 53715
(608) 417-6236
Kling Laboratory
Atrium Basement Meriter Hospital
202 S Park St.
Madison, WI. 53715
(608) 417-5780
Kling Laboratory
Major Research Interests
Our lab’s research goals have been to investigate the developmental and nutritional regulation of erythropoiesis (red blood cells production). This research is important because anemia complicates the clinical care of nearly 30,000 premature neonates in US yearly and effective strategies for combating anemia must be developed. Ill premature neonates develop severe anemia, requiring multiple red blood cell transfusions while hospitalized. Erythropoietin, the primary endocrine hormone stimulating erythropoiesis, is relatively deficient in premature neonates. The drug, erythropoietin, although effective in adult patients, does not eliminate transfusions in premature neonates. Our research seeks to determine why erythropoietin therapy is an ineffective therapy in premature infants. Our research approach is two-pronged. First, we are investigating the interactions of iron and erythropoietin in neonatal and infant erythropoiesis. Delivery of sufficient iron is critical to the efficacy of erythropoietin. Unlike other patient populations, in early infancy, no marker of insufficient cellular iron delivery exists. Second, we are investigating the non-traditional roles of erythropoietin. In early development, we are exploring whether erythropoietin’s erythropoietic role is relatively less important than its other roles. Because erythropoietin exerts local paracrine effects, we are examining the effects of erythropoietin in other tissues (e.g. vascular endothelium, intestine, brain and lung). Erythropoietin is delivered to developing tissues in utero by amniotic fluid and after birth by mammalian milk.
A. To evaluate the interactions between iron and erythropoietin in erythropoiesis. Our early work compared normal plasma erythropoietin levels and indicators of iron status in infants. Additional work showed that excessive cellular iron limits erythropoiesis by inhibiting erythropoietin production in vitro and in vivo (Kling, et al. Br J Haematol 1996 & Al Uzri, et al. 2003). In our newborn rat model of impaired tissue iron delivery, we observed that iron delivery for erythropoiesis was prioritized higher than other key tissues, disrupting normal kidney development (Drake, et al, 2009). We are currently examining placental-fetal iron trafficking in intrauterine growth retarded sheep, because fetal growth retardation impairs tissue iron delivery at the expense of erythrooiesis. Because of this fine line between sufficiency and excess, accurate indices of iron status in premature infants were needed. We examined plasma transferrin receptor, but in early infancy, it correlated with erythropoiesis and not just iron deficiency (Kling, Am J Pediatr Hem/Onc 1998). However, the zinc protoporphyrin/heme ratio (ZnPP/H), a measure of incomplete iron incorporation into the red cells showed more promise (Winzerling & Kling, 2001). We found that ZnPP/H reflects iron status in human cord blood, in large babies born to mothers with diabetes, in premature infants at hospital discharge and in newborn rats (Winzerling & Kling, 2001; Dubuque, et al. 2002; Lott, et al., 2005; Lesser, et al. 2006), but was normal in normal in normal large babies (Kleven, et al. 2006). Because of a need for early identification of impaired iron delivery in newborns, my lab also developed a technique for improving the sensitivity of ZnPP/H (Blohowiak, et al., 2008). Because we found higher levels of ZnPP/H in minority neonates, compared to Caucasian neonates, (Baumann-Blackmore, et al. 2008) we are currently determining if ZnPP/H could be used in a more general sense to screen newborns at birth for iron deficiency (MERC and Thrasher funding).
B. To investigate non-traditional roles of erythropoietin. A reason why the drug, erythropoietin, is ineffective at preventing transfusions in premature infants is that erythropoietin’s role in erythropoiesis is relatively less important than in other tissues. Because milk is a source of biologically important growth factors including erythropoietin, we found that erythropoietin present in mammalian milk is protected from gastrointestinal degradation by milk and is absorbed enterally, reaching local and distal sites(Kling, Pediatr Res 1999; Miller-Gilbert, 2001). An intriguing finding was that milk-borne erythropoietin stimulates vascular growth in intestinal endothelial cells (Ashley, 2002). Feeding erythropoietin stimulated red cell production and increased instestinal growth in suckling rats fed formula deficient in other growth factors (Kling, 2008). One potential reason why erythropoietin is ineffective in preventing transfusions is that erythropoietin’s developmental erythropoietic effects may require interacting with another hematopoietic milk borne growth factor, such as insulin-like growth factor-1 (IGF-1). We found that milk borne IGF-1 stimulated erythropoiesis, not by directly increasing erythropoietin production, but improving iron absorption (Kling, 2006). Better iron status may improve erythropoietin efficacy. The interplay between IGF-1, erythropoietin and iron is intriguing.
 Kling Lab Members |  Midwest Society for Pediatric Research - 2009 |
Staff
 Sharon E. Blohowiak Research Specialist |  Jennifer M. Calmes Research Assistant |  Keri A. Drake Research Assistant |  Beth A. Fischer PhD Scientist |  Karen P. Flores Research Assistant |
 Jason M. Habeck Medical Student |  Sheena S. Hirschfield Research Assistant |  Steven L. Marmer Research Assistant |  Katie M. Meyer Graduate Student |  Alyssa K. Phillips Associate Research Specialist |
 Sheila C. Roy Medical Student |  Vidya Sridhar, MBBS Visiting Assistant Scientist |
Sharon E. Blohowiak
Sharon has been working in the Kling research lab since 2002. She works as the laboratory manager and is responsible for supervision of students, grant management, accounting of lab funds, manuscript submission, and day-to-day laboratory activities. Sharon graduated from UW-Madison in 1996 with a BS in Animal Science and went on to receive her certification and license in secondary biology education. She will be completing her master’s degree in Administrative Leadership in December 2009 from UW-Milwaukee. She lives in Monticello with her husband, 2 sons, 3 cats and 1 dog on a farmette.
Jennifer M. Calmes
Jennifer is a senior at UW Madison majoring in Biology. She hopes to attend Physician Assistant School in May.Jenny has played miscellaneous roles in the lab since her arrival in 2008, but she has recently researched sheep placental tissues and kidney development, as well as rat kidney development and blood pressure.
Keri A. Drake
Keri is a medical student applying for a Pediatrics residency position. Keri will graduate with “Honor’s in Research” in May 2010. Keri has worked in the Kling lab since summer 2007. Keri presented her work at he Midwest Society for Pediatric Research in Indianapolis, October 2007 and the Medical Student Research Symposia in November 2007. She is excited to see her first author paper from her research published in an upcoming issue of the journal, “Pediatrics Research.” The article will be titled, Iron Deficiency and Renal Development.
Beth A. Fischer
Beth was the Iron Deficiency in Infancy Clinical Study Coordinator from 2007-2009 and now manages the data and analysis for the study. She is now Director of Institutional Research and Planning at Zane State College in Ohio. She continues to play a role in all subprojects within the larger study, although her major interest remains whether stress in pregnancy interferes with transport of iron to the fetus.
Karen P. Flores
Karen is a freshman at UW-Madison in the College of Engineering. She plans to major in Biomedical Engineering and attend medical school. She is very interested in cell biology, stem cell research and tissue engineering.
Jason M. Habeck
Jason is a medical student who worked in the Kling lab as an undergraduate (2007-2008) and as a medical student (2009). His work relates to the effects of a sheep uterine restriction model on placental iron transport and renal development in the offspring. Jason presented his work at the Midwest Society for Pediatric Research in Cleveland, October 2008.
Sheena Hirschfield
Sheena is currently an undergraduate student in her fourth year, studying for her biology degree. She hopes to go to medical school in the fall of 2011 to become a Pediatrician. Her research interests include the Pediatric realm of things in general. Sheena is also a phlebotomist for the Iron Deficiency in Infancy Study. Sheena presented her work on maternal stress and fetal iron status at the Midwest Society for Pediatric Research October 2009.
Steven L. Marmer
Steven is a junior in Biochemistry at UW and has worked with the Kling lab since 2008. His project is a subset of the Iron Deficiency in Infancy Study. He is studying whether zinc protoporphyrin/heme ratio (ZnPP/H) can be measured on filter paper spots as part of the state-wide newborn screening program. His work focuses on the biochemical interferences with the test. He presented his work at the Midwest Society for Pediatric Research in October 2009. When not working in the lab, he is a member of the UW Marching Band.
Katie M. Meyer
Katie completed her undergraduate degree in Biology from the University of Wisconsin-Madison in 2004 and is now a graduate student in the Department of Endocrinology and Reproductive Physiology. She works on intrauterine growth retardation and its effects on placental adaptation and organ growth in the ovine model.
Alyssa K. Phillips
Alyssa completed her undergraduate degree in Biology at the University of Wisconsin-Madison in the spring of 2009. During her undergraduate career, she assisted research in the Department of Nutritional Sciences. Nutrition continues to be her main research interest, especially in how it relates to pregnancy and infancy.
Sheila C. Roy
Sheila Roy is a medical student whose research examines the role of maternal obesity in the iron status of newborns. Sheila worked with the laboratory in the summer 2009. Her work was presented as a poster at the Midwest Society for Pediatric Research in Chicago, October 2009.
Vidya Sridhar
Vidya is a visiting physician scientist who joined the lab in late 2008. She has played an important role in coordinating subject data entry and follow-up in the Iron Deficiency in Infancy Study. Vidya assists with the subprojects with the larger study. She has also studies iron-binding proteins in human milk and presented that work at the Midwest Society for Pediatric Research in October 2009.
Active Grants
Delayed Cord Clamping as an Intervention for Infants At-Risk for Iron Deficiency
Meriter Foundation
06/2008-05/2010
Closing the Gap on Pediatric Health Disparities: Discerning the Causes and Consequences of Iron Deficiency in Infancy
UW School of Medicine and Public Health WI Partnership Program Collaborative Health Sciences Program
09/2008-08/2011
Early Screening and Interventions for Iron Deficiency in Infancy
Thrasher Research Fund
05/2009-11/2011
Honors & Awards
| Iowa and Regional Student Representative American Society for Medical Technology/Clinical Laboratory Science |
1979-80 |
| National Student Forum Chairman American Society for Medical Technology/Clinical Laboratory Science |
1980-81 |
| Scholarship Recipient Iowa City Free Medical Clinic |
1985 |
| University of Wisconsin Pediatric Resident Research Award | 1988 |
| UA Award for Service to Pediatric Residents | 1999 |
| UA Award for Service to Family Medicine Residents | 1999 |
| UW Odell Award For Research UW-Madison Department of Pediatrics |
2003 |
| 25 Years Membership with the American Society of Clinical Lab Science | 2005 |
| Madison Magazine’s Top Docs Listing | 2008 |
Recent Publications
Kling PJ. Editorial. Zinc protoporphyrin/heme ratio in premature infants – Has it found its place? J Pediatr 2006:148;8-10.
Kling PJ, Taing KM, Dvorak B, Woodward SS, Grille JG, Philipps AF. Insulin-like growth factor-I stimulates erythropoiesis when administered enterally. Growth Factors 2006:24;218-223.
Lesser KB, Schoel SB, Kling PJ. Elevated zinc protoporphyrin/heme ratios in umbilical cord blood after diabetic pregnancy. J Perinatol 2006:26;671-676.
Kleven KJ, Blohowiak SB, Kling PJ. Zinc protoporphyrin/heme ratios in large for gestation newborns. Neonatology 2007:92:91-95.
Kling PJ. Editorial. Iron supplementation in prematurity: How much is too much? J Pediatr 2007:151;3-4.
Kling PJ, Willeitner A, Dvorak B, Blohowiak SE. Milk-borne erythropoietin and iron stimulate erythropoiesis in suckling rats. J Pediatr Gastroent Nutr 2008:46;202-207.
Kling PJ. Am I going to die? Academic Med 2008:83;567.
Baumann-Blackmore NL, Goetz E, Blohowiak SE, Zaka O, Kling PJ. Cord blood zinc protoporphyrin/heme ratio in minority neonates at-risk for iron deficiency. J Pediatr 2008:153;133-136.
Blohowiak SE, Chen ME, Repyak KS, Baumann-Blackmore NL, Carlton DP, Georgieff MK, Crenshaw TD, Kling PJ. Reticulocyte enrichment of zinc protoporphyrin/heme discriminates impaired iron supply during early development, Pediatr Res 2008:64;63-67.
Drake KA, Sauerbry MJ, Blohowiak SE, Repyak KS, Kling PJ. Iron Deficiency and Renal Development in the Newborn Rat. 2009, Submitted to Pediatr Res.