Pulmonary Biology

Paul Kingma, MD, PhD

Appointment

Assistant Professor of Pediatrics

Email

Phone

(513) 636-2995

Bio

Each day the human lung exchanges approximately 15,000 liters of air that contains a multitude of microorganisms and fine particles. Despite the absence of a rigid protective physical barrier at the air-tissue interface, the lung is infrequently subjected to infection or injury by toxicants. Pulmonary homeostasis is maintained in large part by multilayered innate and acquired immune systems that simultaneously defend ~150 m2 of lung surface area from microbial invasion and maintain the integrity of the alveoli.

My research focuses on Surfactant Protein D (SP-D) which is a critical component of the pulmonary innate immune system and a member of the collectin family of proteins. In the lung, SP-D binds bacterial, viral, and fungal pathogens and facilitates the clearance of these organisms. SP-D also binds inflammatory molecules, such as lipopolysaccharide, and limits the inflammatory damage that these molecules induce. In addition to functioning as a microbial opsonin, animal models of SP-D deficiency revealed that the mice lacking SP-D develop enlarged, foamy macrophages, as well as, gradually worsening pulmonary emphysema and accumulations of abnormal surfactant phospholipid. These models indicate that SP-D has a complex role in lung immunity and surfactant homeostasis. As a consequence of its role in the lung immune system, SP-D is being developed as a therapeutic agent against a variety of pulmonary conditions including infection, emphysema, surfactant degradation, and bronchopulmonary dysplasia. Current projects in my lab center around two primary goals. The first is to determine the mechanisms by which structural regions of SP-D control immune cell activation and surfactant homeostasis in the lung. The second is to determine the role of SP-D in the systemic innate immune system and if the unique properties of SP-D can be utilized in treating systemic infection and sepsis.

Credentials

BS Calvin College, Biology and Chemistry, 1992

MD,PhD Vanderbilt University, Medicine and
Biochemistry, 2000

Pediatric Residency Cincinnati Children's Hospital Medical Center, 2003

Neonatal Fellowship Cincinnati Children's Hospital Medical Center, 2005

Position History

1992-2000 Medical Scientist Training Program, Vanderbilt University

1994-1997 Graduate Research Assistant in Biochemistry, Vanderbilt University

1997-1998 Postdoctoral Fellow in the Department of Biochemistry, Vanderbilt University

2000-2003 Resident Physician, Cincinnati Children's Hospital Medical Center

2003-2005 Fellowship in Neonatology, Cincinnati Children's Hospital Medical Center

2005-present Assistant Professor, Cincinnati Children's Hospital Medical Center

Awards and Honors

1995 Dissertation Enhancement Grant, Vanderbilt University

1997 ASBMB Young Scientist Travel Fellowship

2000 John G. Coniglio Prize in Biochemistry, Vanderbilt University

2003 Neonatology Award, Cincinnati Children's Hospital Medical Center

2004 Reginald Tsang Award, Cincinnati Children's Hospital Medical Center

Research Grants and Contracts

Translational Research Initiative CCHMC (Kingma) 07/01/06 - 06/30/07

Surfactant Protein D in Systemic Infection and Inflammation

The major goal of this pilot project is to evaluate the potential of surfactant protein D to be used as a human therapeutic agent in systemic infection. The specific goals are: 1) To determine if SP-D reduces LPS-induced systemic inflammation, 2) To determine if SP-D reduces inflammation in systemic infection, 3) To determine the tissue location of systemic SP-D clearance.

Publications, Most Recent

Kingma, PS, Corbett, AH, Burcham, PC, Marnett, LJ and Osheroff, N. (1995) J. Biol. Chem. 270, 21441-21444 (Communication). "Abasic Sites Stimulate Double-Stranded DNA Cleavage Mediated by Topoisomerase II: DNA Lesions as Endogenous Topoisomerase II Poisons"

Burden, DA, Kingma, PS, Froelich-Ammon, SJ, Bjornsti, MA, Patchan, MW, Thompson, RB, and Osheroff, N. (1996) J. Biol. Chem. 271, 29238-29244 "Topoisomerase II-Etoposide Interactions Direct the Formation of Drug-Induced Enzyme-DNA Cleavage Complexes"

Kingma, PS, and Osheroff, N. (1997) J. Biol. Chem. 272, 1148-1155. "Apurinic Sites are Position-Specific Topoisomerase II Poisons"

Kingma, PS, and Osheroff, N. (1997) J. Biol. Chem., 272, 7488-7493. "Spontaneous DNA Damage Stimulates Topoisomerase II-Mediated DNA Cleavage"

Kingma, PS, Greider, CA, and Osheroff, N. (1997) Biochemistry, 36, 5934-5930, "Spontaneous DNA Lesions Poison Human Topoisomerase IIx and Stimulate Cleavage Proximal to Leukemic 11q23 Chromosomal Break Points"

Kingma, PS and Osheroff, N. (1998) J. Biol. Chem. 273, 17999-18002 "Topoisomerase II-mediated DNA Cleavage and Religation in the Absence of Base Pairing: Abasic Lesions as a Tool to Dissect Enzyme Mechanism"

Kingma, PS, Burden, DA, and Osheroff, N. (1999) Biochemistry, 38, 3457-3461, "Binding of Etoposide to Topoisomerase II in the Absence of DNA: Decreased Affinity as a mechanism of Drug Resistance"

Bjergbaek L, Kingma P, Nielsen, IS, Wang, Y, Westergaard, O, Osheroff, N, Andersen, AH. (2000) J. Biol. Chem. 275, 13041-13048 "Communication between the ATPase and cleavage/religation domains of human topoisomerase IIalpha"

Kingma, PS, Zhang, L, Ikegami, M, Hartshorn, K, McCormick, F, and Whitsett, JA. (2006) J. Biol. Chem. 281, 24496-24505, "Correction of Pulmonary Abnomalities in Sftpd-/- Mice Requires the Collagenous Domain of Surfactant Protein D"