Instructor in Medicine
Harvard Medical School, Brigham and Women’s Hospital
Peter G. Czarnecki, MD studies the function of ciliopathy proteins and the role of pathogenic mutations. He analyzes the assembly of ciliary protein complexes into functional modules using protein biochemistry, cell biology and live cell imaging techniques. Dr. Czarnecki’s interest in ciliary biology and the connections to Polycystic Kidney Disease pathogenesis range back to his time as a student at the University of Freiburg Medical School (Germany). He worked in the laboratory of Gerd Walz (Freiburg), before moving on to his residency training in Internal Medicine at the Mayo Clinic in Rochester, MN. At the Mayo Clinic, he pursued further training in PKD genetics and ciliary biology, working at the Mayo PKD center under the mentorship of Peter C. Harris. Dr. Czarnecki completed his clinical training in Nephrology at the Beth Israel Deaconess Medical Center (BIDMC), and he had a broad exposure to clinical management of PKD, working closely with Ted I. Steinman. Together with Dr. Steinman, Dr. Czarnecki conducted a number of clinical research studies, most importantly the BIDMC branch of the HALT-PKD study, the largest ADPKD-related clinical trial ever performed. Dr. Czarnecki maintained a strong involvement in basic research in ciliary biology throughout his fellowship, and worked in the Laboratory of Quantitative Cell Biology under the supervision of Jagesh V. Shah.
Ciliopathy Signaling
Dr. Czarnecki continues his experimental work on ciliopathy proteins at the Laboratory of Quantitative Cell Biology with Dr. Shah. His special interest is the ciliary Inversin compartment, a protein module at the basal ciliary axoneme that is composed of four known ciliopathy proteins, inversin, NPHP3, NEK8 and ANKS6. Dr. Czarnecki investigates the assembly pathway of this multiprotein complex, the downstream effects of mutations affecting these proteins, and the consequences of ciliary signaling pathways. He discovered a phosphorylation-dependent mechanism involving the NEK8 protein kinase in association with its allosteric activator, ANKS6, that plays a crucial role in early embryonic patterning of kidneys, cardiovascular system and L-/R-asymmetry determination.
BWH PKD clinic
In 2014, Dr. Czarnecki joined the Brigham and Women’s Hospital staff as Associate Physician with the Division of Renal Medicine and Instructor of Medicine at Harvard Medical School. He started a supspecialty clinic specifically devoted to Polycystic Kidney Disease, as well as related genetic and cystic kidney disorders. Dr. Czarnecki offers primary evaluation and longitudinal follow-up of patients with PKD, second opinions, genetic counseling, and the participation in epidemiologic and therapeutic studies. Dr. Czarnecki provides adult Nephrology follow-up of former Pediatric Nephrology patients with genetic and cystic kidney diseases, like Nephronophthisis, CAKUT-spectrum disorders and complex ciliopathy syndromes. In addition, Dr. Czarnecki offers Nephrology (co-)management of patients with von-Hippel-Lindau disease, Tuberous Sclerosis, as well as primary evaluation of renal cysts.
Publications
Czarnecki PG, Gabriel GC, Manning DK, Sergeev M, Lemke K, Klena NT, Liu X, Chen Y, Li Y, San Agustin JT, Garnaas MK, Francis RJ, Tobita K, Goessling W, Pazour GJ, Lo CW, Beier DR, Shah JV: “ANKS6 is the critical activator of NEK8 kinase in embryonic situs determination and organ patterning”, Nat Commun. 2015 Jan 20;6:6023. PMID: 25599650
Schrier RW, Abebe KZ, Perrone RD, Torres VE, Braun WE, Steinman TI, Winklhofer FT, Brosnahan G, Czarnecki PG, Hogan MC, Miskulin DC, Rahbari-Oskoui FF, Grantham JJ, Harris PC, Flessner MF, Ty Bae K, Moore CG and Chapman AB for the HALT PKD Study Group: “Angiotensin Blockade, Blood Pressure, and Autosomal Dominant Polycystic
Torres VE, Abebe KZ, Chapman AB, Schrier RW, Braun WE, Steinman TI, Winklhofer FT, Brosnahan G, Czarnecki PG, Hogan MC, Miskulin DC, Rahbari-Oskoui FF, Grantham JJ, Harris PC, Flessner MF, Moore CG and Perrone RD for the HALT PKD Study Group: “Angiotensin Blockade in Late Autosomal Dominant Polycystic Kidney Disease”, N Engl J Med. 2014 Dec 11;371(24):2267-76. PMID: 25399731
Riella C, Czarnecki PG, Steinman TI: “Therapeutic Advances in the Treatment of Polycystic Kidney Disease”, Nephron Clin Pract. 2014;128(3-4):297-302. PMID: 25573484
Czarnecki PG and Steinman TI: “Polycystic kidney disease: new horizons and therapeutic frontiers”, Minerva Urol Nefrol. 2013 Mar;65(1):61-8. PMID: 23538311
Czarnecki PG and Steinman TI: “Pain and pain management in Polycystic Kidney Disease” in Gattone VH and Bacallao RL, “Polycystic Kidney Disease: from Bench to Bedside”, Mar 2013, Future Medicine Ltd., doi: 10.2217/9781780841748, eISBN (PDF): 978-1-78084-174-8
Halbritter J, Bizet AA, Schmidts M, Porath JD, Braun DA, Gee HY, McInerney-Leo AM, Krug P, Filhol E, Davis EE, Airik R, Czarnecki PG, Lehman AM, Trnka P, Nitschké P, Bole-Feysot C, Schueler M, Knebelmann B, Burtey S, Szabó AJ, Tory K, Leo PJ, Gardiner B, McKenzie FA, Zankl A, Brown MA, Hartley JL, Maher ER, Li C, Leroux MR, Scambler PJ, Zhan SH, Jones SJ, Kayserili H, Tuysuz B, Moorani KN, Constantinescu A, Krantz ID, Kaplan BS, Shah JV; UK10K Consortium, Hurd TW, Doherty D, Katsanis N, Duncan EL, Otto EA, Beales PL, Mitchison HM, Saunier S, Hildebrandt F.: “Defects in the IFT-B Component IFT172 Cause Jeune and Mainzer-Saldino Syndromes in Humans”, Am J Hum Genet. 2013 Nov 7;93(5):915-25. PMID: 24140113
Leightner AC, Hommerding CJ, Peng Y, Salisbury JL, Gainullin VG, Czarnecki PG, Sussman CR and Harris PC: “The Meckel syndrome protein meckelin (TMEM67) is a key regulator of cilia function, but is not required for tissue planar polarity”, Human Molecular Genetics 2013 May 15;22(10):2024-40, PMID: 23393159
Czarnecki PG and Shah JV: “The ciliary transition zone: From Morphology and Molecules to Medicine”, Trends Cell Biol 2012, Apr 22(4):201-10, PMID 22401885
Hopp K, Heyer CM, Hommerding CJ, Henke SA, Sundsbak JL, Patel S, Patel P, Consugar MB, Czarnecki PG, Gliem TJ, Torres VE, Rossetti S, Harris PC: “B9D1 is revealed as a novel Meckel syndrome (MKS) gene by targeted exon-enriched next-generation sequencing and deletion analysis” Hum Mol Genet 2011, Jul 20(13):2524-34, PMID: 21493627
Harris PC, Czarnecki PG: “Ziliopathien”, “Ciliopathies” (German), review, Medizinische Genetik 2009, Feb 21(1):14-20, doi: 10.1007/s11825-009-0144-0
Tammachote R, Hommerding CJ, Sinders RM, Miller CA, Czarnecki PG, Leightner AC, Salisbury JL, Ward CJ, Torres VE, Gattone VH 2nd, Harris PC: “Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3”, Hum Mol Genet 2009, Sep 18(17):3311-23, PMID: 19515853
Czarnecki PG, Lager DJ, Leung N, Dispenzieri A, Cosio FG, Fervenza FC: “Long-term outcome of kidney transplantation in patients with fibrillary glomerulonephritis and in patients with monoclonal gammopathy and fibrillary deposits”, Kidney International 2009, Feb;75(4):420-7, PMID: 19037251
Schäfer T, Pütz M, Lienkamp S, Ganner A, Bergbreiter A, Ramachandran H, Gieloff V, Gerner M, Mattonet C, Czarnecki PG, Sayer JA, Otto EA, Hildebrandt F, Kramer-Zucker A, Walz G: “Genetic and physical interaction between the NPHP5 and NPHP6 gene products”, Hum Mol Genet 2008, Dec 17(23):3655-62, PMID: 18723859