430 Clinical Research Building | 415 Curie Blvd. | University of Pennsylvania | Philadelphia PA 19104-6145

Bart Ferwerda, Ph.D.

Postdoctoral Fellow

Department of Genetics
School of Medicine
University of Pennsylvania
422 Clinical Research Building
415 Curie Blvd
Philadelphia, PA 19104-6145

ferwerda@mail.med.upenn.edu

Research

Education

Grants and Scholarships

Publications

Presentations

Research

The human innate immune system has evolved under continuous pressure from a wide range of pathogens. During human history this has resulted in selection of specific variants of genes from the innate immune system, which were beneficial under those pathogenic pressures. With evolutionary analysis of these regions it is possible to find these signatures of selection. Due to the human origin in Africa with high genetic diversity on this continent, this project will focus on African populations. The main objective is to assess variations in loci involved in the innate immune system in African populations and identify signatures of selection due to infectious pressure in order to identify potential functional variants that play a role in resistance to disease. A complementary approach will be initiated, that will combine evolutionary genetic modelling and field studies assessing the functional consequences of the genetic variants.

The combination of studying evolutionary genetic signatures and functional consequences for the innate immune system will provide insight about how variants at these loci play a role in susceptibility of individuals to important infectious diseases. In addition this knowledge can provide novel information that can eventually be used for better treatment against life-threatening infections in African populations.

Education

Ph.D.

Department of Internal Medicine and Nijmegen Institute for Infection, Inflammation, and Immunity (N4I), Radboud University Nijmegen, Nijmegen, The Netherlands. March 2010. Cum Laude. Title: Genetic variation in the innate immune system and susceptibility to infections. Advisors: Prof Dr. Mihai G. Netea and Prof. Dr. Jos WM van der Meer.

Collaborations projects during Ph.D.:
Cultural and linguistic evolution.
Professor Michael Dunn and Dr Dan Dediu from the Max Planck institute for psycholinguistics, Departament of evolutionary processes in language and culture, Nijmegen, the Netherlands

The Genographic project: Western/Central Europe region.
Professor Jaume Bertranpetit and Dr David Comes from the Unitat de Biologia Evolutiva, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain

Dectin-1 polymorphisms and their effect on the innate immune signaling.
Professor Gordon D. Brown of the Institute of Infectious Disease and Molecular Medicine, UCT Faculty Of Health Sciences, Cape Town, South Africa                              

B.S & B.A.

Biology, Vrije Universiteit Amsterdam

Grands and Scholarships

Rubicon grant of the Netherlands Organisation for Scientific Research (NWO)

Peer Reviewed Publications

Zhernakova A,Elbers C.C., Ferwerda B, Romanos J, Trynka G, Dubois P.C., de Kovel C.G.F., Oosting M, Barisani D, Bardella M.T., Finnish Celiac Disease Study Group, Joosten L.A.B, Saavalainen P, van Heel D A., Catassi C, Netea M G., Wijmenga C. Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection. Am J Hum Genet. 2010 Jun2.

Plantinga TS, Hamza OJ, Willment JA, Ferwerda B, van de Geer NM, Verweij PE, Matee MI, Banahan K, O'neill LA, Kullberg BJ, Brown GD, van der Ven AJ, Netea MG. Genetic variation of innate immune genes in HIV-infected african patients with or without oropharyngeal candidiasis. J Acquir Immune Defic Syndr. 2010 Sep 1;55(1):87-94.

Kumpf O, Giamarellos-Bourboulis EJ, Koch A, Hamann L, Mouktaroudi M, Oh DY, Latz E, Lorenz E, Schwartz DA, Ferwerda B, Routsi C, Skalioti C, Kullberg BJ, van der Meer JW, Schlag PM, Netea MG, Zacharowski K, Schumann RR. Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts. Crit Care. 2010;14(3):R103. Epub 2010 Jun 3.

Papadopoulos AI, Ferwerda B, Antoniadou A, Sakka V, Galani L, Kavatha D, Panagopoulos P, Poulakou G, Kanellakopoulou K, van der Meer JW, Giamarellos-Bourboulis EJ, Netea MG. Association of toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms with increased infection risk in patients with advanced HIV-1 infection. Clin Infect Dis. 2010 Jul 15;51(2):242-7.

McCall MB, Ferwerda B, Hopman J, Ploemen I, Maiga B, Daou M, Dolo A, Hermsen CC, Doumbo OK, Bedu-Addo G, van der Meer JW, Troye-Blomberg M, van der Ven AJ, Schumann RR, Sauerwein RW, Mockenhaupt FP, Netea MG. Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations. Eur Cytokine Netw. 2010 Jun 1;21(2):77-83. Epub 2010 Apr 27.

Ferwerda B, Ferwerda G, Plantinga T, Willment J.A., van Spriel A.B., Venselaar H, Elbers C.C., Cambi A, Huysamen C, Jacobs L, Jansen T, Verheijen K, Masthoff L, Morre S.A., Vriend G,. Williams D.L, Joosten L.A.B., Wijmenga C, van der Meer J.W.M., Adema, G.J., Kulberg BJ, Brown G.D., Netea M.G. A family with human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med. 2009 Oct 29;361(18):1760-7

Ferwerda B, McCall MB, de Vries MC, Hopman J, Maiga B, Dolo A, Doumbo O, Daou M, de Jong D, Joosten LA, Tissingh RA, Reubsaet FA, Sauerwein R, van der Meer JW, van der Ven AJ, Netea MG. Caspase-12 and the inflammatory response to Yersinia pestis. PLoS One. 2009 Sep 1;4(9):e6870.

Plantinga TS, van der Velden WJ, Ferwerda B, van Spriel AB, Adema G, Feuth T, Donnelly JP, Brown GD, Kullberg BJ, Blijlevens NM, Netea MG. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2009 Sep 1;49(5):724-32.

Ferwerda B, Alonso S, Banahan K, McCall MB, Giamarellos-Bourboulis EJ, Ramakers BP, Mouktaroudi M, Fain PR, Izagirre N, Syafruddin D, Cristea T, Mockenhaupt FP, Troye-Blomberg M, Kumpf O, Maiga B, Dolo A, Doumbo O, Sundaresan S, Bedu-Addo G, van Crevel R, Hamann L, Oh DY, Schumann RR, Joosten LA, de la Rúa C, Sauerwein R, Drenth JP, Kullberg BJ, van der Ven AJ, Hill AV, Pickkers P, van der Meer JW, O'Neill LA, Netea MG. Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock. Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10272-7. Epub 2009 Jun 9.

de Mast Q, Groot E, Asih PB, Syafruddin D, Oosting M, Sebastian S, Ferwerda B, Netea MG, de Groot PG, van der Ven AJ, Fijnheer R. ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria. Am J Trop Med Hyg. 2009 Mar;80(3):492-498.

Ferwerda B, McCall MB, Verheijen K, Kullberg BJ, van der Ven AJ, Van der Meer JW, Netea MG. Functional consequences of toll-like receptor 4 polymorphisms. Mol Med. 2008 May-Jun;14(5-6):346-352. Review.

Ferwerda B, McCall MB, Alonso S, Giamarellos-Bourboulis EJ, Mouktaroudi M, Izagirre N, Syafruddin D, Kibiki G, Cristea T, Hijmans A, Hamann L, Israel S, ElGhazali G, Troye-Blomberg M, Kumpf O, Maiga B, Dolo A, Doumbo O, Hermsen CC, Stalenhoef AF, van Crevel R, Brunner HG, Oh DY, Schumann RR, de la Rúa C, Sauerwein R, Kullberg BJ, van der Ven AJ, van der Meer JW, Netea MG. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16645-50. Epub 2007 Oct 9.

Ferwerda B, Kibiki GS, Netea MG, Dolmans WM, van der Ven AJ. The toll-like receptor 4 Asp299Gly variant and tuberculosis susceptibility in HIV-infected patients in Tanzania. AIDS. 2007 Jun 19;21(10):1375-1377.

Timmermans MJ, Ellers J, Mariën J, Verhoef SC, Ferwerda B, van Straalen NM. Genetic structure in Orchesella cincta (Collembola): strong subdivision of European populations inferred from mtDNA and AFLP markers. Mol Ecol. 2005 Jun;14(7):2017-24.

Kools SA, Ferwerda B, van Gestel CA, van Straalen NM. Microbial responses to zinc in soil microcosms with and without a natural assemblage of enchytraeids. Environ Toxicol Chem. 2005 Sep; 24(9):2178-84.

Presentations

2010

June
Out of Africa: Evolution and immunogenetics of the innate immune system. (Presentation)
Invited speaker, First Dutch infection disease day, The Netherlands.

2009

November
Clinical and evolutionary effects of genetic variation in the innate immune system on pathogenic susceptibility. (Presentation) Academic Medical Centrum Amsterdam Masterclass Svante Pääbo Amsterdam, The Netherlands.

October
Caspase-12 and the inflammatory response to Yersinia pestis (Poster). ASHG 2009, Honolulu/Hawaii, USA.

May
Evolutionary pressures of Gram-Negative bacterial infections on the Toll-like receptor 4 signaling pathway (Presentation). Invited speaker, Royal Netherlands Academy of Arts and Sciences (KNAW), Darwin meeting for young scientist, Amsterdam, The Netherlands.

February
The role of genetic predisposition for the pathogenesis of sepsis (Presentation). Invited speaker, Workshop of the Hellenic sepsis study group, Athens, Greece.

2008

September
Ancient infectious evolutionary pressure on functional variants of the Mal/TIRAP gene (Poster). Toll2008, Lisabon/Cascais, Portugal.

April
Dectin-1 polymorphisms are associated with a higher susceptibility to mucosal candida (Presentation). NUCI, Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen,The Netherlands.

March
TLR4 polymorphisms and the effect of polymorphisms on the susceptibility of infectious diseases (Master clas). The KNAW conference on: The role of DNA polymorphisms in complex traits and disease. Royal Netherlands Academy of Arts and Sciences Amsterdam, The Netherlands.

2007

October
TLR4 polymorphisms, infectious diseases and evolutionary pressure during migration of modern humans (Poster). Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Chigaco, USA.

May
TLR4 polymorphisms and the effect of polymorphisms on the susceptibility of infectious diseases (Presentation). Netherlands Inflammation network (NIN), Lunteren, The Netherlands.