D J Kwiatkowski

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Functions of gelsolin: motility, signaling, apoptosis, cancer
    D J Kwiatkowski
    Genetics Laboratory Hematology Division Brigham and Women s Hospital 221 Longwood Avenue Boston MA 02115 USA
    Curr Opin Cell Biol 11:103-8. 1999
  2. ncbi request reprint Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications
    D J Kwiatkowski
    Division of Experimental Medicine, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Clin Oncol 16:2468-77. 1998
  3. ncbi request reprint Human XPMC2H: cDNA cloning, mapping to 9q34, genomic structure, and evaluation as TSC1
    J Kwiatkowska
    Experimental Medicine Division, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Genomics 44:350-4. 1997
  4. pmc Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs
    S L Dabora
    Genetics Laboratory, Division of Hematology, Brigham and Women s Hospital, Boston, MA, 02115, USA
    Am J Hum Genet 68:64-80. 2001
  5. ncbi request reprint Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1
    D Humphrey
    Experimental Medicine Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Ann Hum Genet 61:299-305. 1997
  6. ncbi request reprint Influence of genetic variation in the C-reactive protein gene on the inflammatory response during and after acute coronary ischemia
    J Suk Danik
    The Donald W Reynolds Center for Cardiovascular Research, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02115, USA
    Ann Hum Genet 70:705-16. 2006
  7. ncbi request reprint Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance
    J Kwiatkowska
    Division of Experimental Medicine and Medical Oncology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Ann Hum Genet 62:277-85. 1998
  8. pmc Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing
    W Witke
    Hematology Division, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Cell Biol 154:775-84. 2001
  9. ncbi request reprint Advillin (p92): a new member of the gelsolin/villin family of actin regulatory proteins
    P W Marks
    Division of Experimental Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Cell Sci 111:2129-36. 1998
  10. ncbi request reprint Differential developmentally regulated expression of gelsolin family members in the mouse
    M Arai
    Genetics Laboratory, Hematology Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Dev Dyn 215:297-307. 1999

Detail Information

Publications51

  1. ncbi request reprint Functions of gelsolin: motility, signaling, apoptosis, cancer
    D J Kwiatkowski
    Genetics Laboratory Hematology Division Brigham and Women s Hospital 221 Longwood Avenue Boston MA 02115 USA
    Curr Opin Cell Biol 11:103-8. 1999
    ..Gelsolin is an obligate downstream effector of Rac for motility in dermal fibroblasts, regulates phosphoinositide signaling pathways and ion channel function in vivo, and acts as both a regulator and effector of apoptosis...
  2. ncbi request reprint Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications
    D J Kwiatkowski
    Division of Experimental Medicine, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Clin Oncol 16:2468-77. 1998
    ..To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design a molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC)...
  3. ncbi request reprint Human XPMC2H: cDNA cloning, mapping to 9q34, genomic structure, and evaluation as TSC1
    J Kwiatkowska
    Experimental Medicine Division, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Genomics 44:350-4. 1997
    ..Through SSCP and heteroduplex analysis of genomic DNA, we found two intragenic polymorphisms but no evidence for significant mutations in patients with tuberous sclerosis in this gene...
  4. pmc Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs
    S L Dabora
    Genetics Laboratory, Division of Hematology, Brigham and Women s Hospital, Boston, MA, 02115, USA
    Am J Hum Genet 68:64-80. 2001
    ....
  5. ncbi request reprint Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1
    D Humphrey
    Experimental Medicine Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Ann Hum Genet 61:299-305. 1997
    ....
  6. ncbi request reprint Influence of genetic variation in the C-reactive protein gene on the inflammatory response during and after acute coronary ischemia
    J Suk Danik
    The Donald W Reynolds Center for Cardiovascular Research, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02115, USA
    Ann Hum Genet 70:705-16. 2006
    ..Assessment of CRP genetic variants identified patients with higher and lower CRP elevation after acute coronary syndrome...
  7. ncbi request reprint Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance
    J Kwiatkowska
    Division of Experimental Medicine and Medical Oncology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Ann Hum Genet 62:277-85. 1998
    ..The observations indicate that TSC1 mutations are all inactivating, suggest that TSC1 disease occurs in only 15-20% of the sporadic TSC population, and demonstrate that presymptomatic TSC does occur...
  8. pmc Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing
    W Witke
    Hematology Division, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Cell Biol 154:775-84. 2001
    ..These primary effects on macrophage motile function suggest that CapG may be a useful target for the regulation of macrophage-mediated inflammatory responses...
  9. ncbi request reprint Advillin (p92): a new member of the gelsolin/villin family of actin regulatory proteins
    P W Marks
    Division of Experimental Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Cell Sci 111:2129-36. 1998
    ..5 in cerebral cortex. We propose that p92 (advillin) has unique functions in the morphogenesis of neuronal cells which form ganglia, and that it may compensate to explain the near normal phenotype observed in villin-deficient mice...
  10. ncbi request reprint Differential developmentally regulated expression of gelsolin family members in the mouse
    M Arai
    Genetics Laboratory, Hematology Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Dev Dyn 215:297-307. 1999
    ..dev dyn 1999;215:297-307...
  11. ncbi request reprint Superiority of denaturing high performance liquid chromatography over single-stranded conformation and conformation-sensitive gel electrophoresis for mutation detection in TSC2
    Y S Choy
    Division of Hematology, Brigham and Women Hospital, Boston, Massachussetts 02115, USA
    Ann Hum Genet 63:383-91. 1999
    ..We conclude that DHPLC is superior to both CSGE and SSCP for detection of DNA sequence variation in TSC2, particularly for single base substitution mutations...
  12. pmc Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background
    H Onda
    Genetics Laboratory, Hematology Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 104:687-95. 1999
    ....
  13. pmc Somatic mosaicism is rare in unaffected parents of patients with sporadic tuberous sclerosis
    P S Roberts
    Hematology Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Med Genet 41:e69. 2004
  14. ncbi request reprint The actin-binding proteins adseverin and gelsolin are both highly expressed but differentially localized in kidney and intestine
    A Lueck
    Brigham and Women s Hospital, Harvard Medical School, Department of Medicine, Division of Experimental Medicine, Boston, MA 02115, USA
    J Cell Sci 111:3633-43. 1998
    ..The observations indicate high level expression of adseverin in specific cells of the kidney and colon, and suggest a previously unrecognized function of adseverin in epithelial cell function...
  15. pmc TSC1 loss synergizes with KRAS activation in lung cancer development in the mouse and confers rapamycin sensitivity
    M C Liang
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
    Oncogene 29:1588-97. 2010
    ..Rapamycin may have unique benefit for patients with lung cancer, for whom the TSC1/TSC2 function is limited...
  16. ncbi request reprint Comprehensive mutation analysis of TSC1 using two-dimensional DNA electrophoresis with DGGE
    S L Dabora
    Division of Hematology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Ann Hum Genet 62:491-504. 1998
    ..During this study, we identified 2 new mutations (exon 8 and exon 15), a new polymorphism (intron 4), and the first variant identified in a non-coding exon (exon 2)...
  17. ncbi request reprint Qualitative and quantitative effects of APOE genetic variation on plasma C-reactive protein, LDL-cholesterol, and apoE protein
    D I Chasman
    Division of Preventive Medicine and Center for Cardiovascular Disease Prevention, Brigham and Women s Hospital, Boston, MA 02215, USA
    Genes Immun 7:211-9. 2006
    ..Quantitative analysis suggested that the effect on CRP is more likely a consequence of intrinsic functional differences among the E2, E3, and E4 apoE proteins than different levels of apoE protein or LDL-C in the plasma...
  18. ncbi request reprint Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28
    J B Gorlin
    Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts
    Genomics 17:496-8. 1993
    ..The FLN gene is found within a 200-kb region centromeric to the G6PD locus and telomeric to DSX52 and the color vision locus...
  19. ncbi request reprint Genetic determinants of C-reactive protein in COPD
    C P Hersh
    Channing Laboratory, Pulmonary Critical Care Division, Brigham and Women s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA
    Eur Respir J 28:1156-62. 2006
    ..Preliminary evidence suggests an association of the surfactant protein B gene with systemic inflammation in chronic obstructive pulmonary disease...
  20. ncbi request reprint Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1
    E P Henske
    Division of Experimental Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Ann Hum Genet 59:25-37. 1995
    ..VAV2 is likely to serve a similar role more generally in mammalian cells, but is not the TSC1 gene...
  21. ncbi request reprint Cdc42 is required for PIP(2)-induced actin polymerization and early development but not for cell viability
    F Chen
    Departments of Genetics, The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 10:758-65. 2000
    ..Also, whereas genetic analyses have shown that Cdc42 is essential for cell viability in yeast, its potential roles in the growth and development of mammalian cells have not been directly assessed...
  22. ncbi request reprint Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease
    O S Breathnach
    Lowe Center for Thoracic Oncology, Division of Experimental Medicine, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 121:42-7. 2001
    ..Further research is warranted to define the etiology, clinical course, and molecular abnormalities in patients with bronchioloalveolar carcinoma to generate more effective therapeutic approaches...
  23. ncbi request reprint Tuberous sclerosis: from tubers to mTOR
    D J Kwiatkowski
    Hematology Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Ann Hum Genet 67:87-96. 2003
    ..Epistasis experiments and a variety of biochemical studies that followed have indicated a critical function for these proteins in the highly conserved PI-3-kinase-Akt-mTOR signalling pathway...
  24. ncbi request reprint A high-resolution linkage map of human 9q34.1
    E P Henske
    Division of Experimental Medicine and Hematology Oncology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115
    Genomics 17:587-91. 1993
    ..The map should prove useful in analysis of families segregating dystonia and tuberous sclerosis, as the DYT1 and TSC1 loci map within this region...
  25. ncbi request reprint Genomic organization and chromosomal location of murine Cdc42
    P W Marks
    Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Genomics 38:13-8. 1996
    ..Using single-strand conformation polymorphism analysis of a mouse backcross panel, the gene encoding cdc42 has been localized to distal chromosome 4...
  26. ncbi request reprint Distinct biochemical characteristics of the two human profilin isoforms
    R Gieselmann
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Eur J Biochem 229:621-8. 1995
    ..Potential structural differences of profilin I and profilin II that might explain the difference in actin binding are discussed...
  27. pmc Distinct clinical characteristics of tuberous sclerosis complex patients with no mutation identified
    S E Camposano
    Carol and James Herscot Center for Tuberous Sclerosis Complex, Department of Neurology, Massachusetts General Hospital, 175 Cambridge Street, Boston, MA 02114, USA
    Ann Hum Genet 73:141-6. 2009
    ..We suggest that the mechanisms of disease in these patients include both mosaicism for a TSC2 mutation, and unusual non-coding region mutations in TSC2...
  28. ncbi request reprint Association of common CRP gene variants with CRP levels and cardiovascular events
    D T Miller
    Division of Hematology, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Ann Hum Genet 69:623-38. 2005
    ..001). Taken together, these data imply significant interactions between both genetic and environmental contributions to the increased CRP levels that predict a greater risk of future atherothrombotic events in epidemiological studies...
  29. pmc Amplification of EGFR T790M causes resistance to an irreversible EGFR inhibitor
    D Ercan
    Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Oncogene 29:2346-56. 2010
    ..These findings can be used to guide studies of patient tumor specimens from ongoing clinical trials of irreversible EGFR kinase inhibitors...
  30. ncbi request reprint Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin
    W Witke
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 81:41-51. 1995
    ..Neither gelsolin nor other proteins with similar actin filament-severing activity are expressed in early embryonic cells, indicating that this mechanism of actin filament dynamics is not essential for motility during early embryogenesis...
  31. pmc Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions
    Y Niida
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA
    Am J Hum Genet 69:493-503. 2001
    ....
  32. ncbi request reprint A family with seizures and minor features of tuberous sclerosis and a novel TSC2 mutation
    S E O'Connor
    University of Chicago Hospitals, Chicago, IL, USA
    Neurology 61:409-12. 2003
    ..Mutational analysis of TSC2 indicated the presence of the novel missense change 3106T-->C, 1036S-->P in all family members with seizures. The findings suggest that this mild variant form of TSC is due to a novel TSC2 mutation...
  33. ncbi request reprint Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma
    K Tantisira
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Genes Immun 5:343-6. 2004
    ..Although replication of this finding in other, larger samples is needed, variation in TLR6 may have relevance to the pathogenesis of immunologically mediated diseases...
  34. ncbi request reprint Human profilin. Molecular cloning, sequence comparison, and chromosomal analysis
    D J Kwiatkowski
    Department of Medicine, Massachusetts General Hospital, Boston
    J Biol Chem 263:5910-5. 1988
    ..In addition, 5' and 3' untranslated regions are conserved between humans and rodents, implying a functional role for these regions of the profilin gene...
  35. ncbi request reprint Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain
    D J Kwiatkowski
    Nature 323:455-8. 1986
    ..Southern blot analysis indicates that a single gene in the haploid genome encodes both protein forms...
  36. pmc Localization of gelsolin proximal to ABL on chromosome 9
    D J Kwiatkowski
    Department of Medicine, Massachusetts General Hospital, Boston 02114
    Am J Hum Genet 42:565-72. 1988
    ..These studies and standard Southern blot analysis of digested DNA also indicate that the NotI restriction site contained in the gelsolin gene is uncleavable in DNA from white blood cells and hematopoietic cell lines...
  37. pmc Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring
    J B Gorlin
    Department of Medicine, Massachusetts General Hospital, Charlestown
    J Cell Biol 111:1089-105. 1990
    ..The large size of the leaves, their interruption by two hinges and flexible actin-binding site, facilitate cross-linking of widely dispersed actin filaments...
  38. pmc Cloning and chromosomal localization of the human cytoskeletal alpha-actinin gene reveals linkage to the beta-spectrin gene
    H Youssoufian
    Whitehead Institute for Biomedical Research, Cambridge, MA
    Am J Hum Genet 47:62-72. 1990
    ....
  39. ncbi request reprint The human actin-regulatory protein cap G: gene structure and chromosome location
    V S Mishra
    Division of Infectious Diseases, University of Florida College of Medicine, Gainesville 32610
    Genomics 23:560-5. 1994
    ..Further comparisons of these three genes, however, indicate that the evolutionary steps resulting in human gelsolin and villin are likely to have been more complex than a simple tandem duplication of the Cap G gene...
  40. ncbi request reprint Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients
    P J Wilson
    Molecular Neurogenetics Unit, MGH East, Charlestown, MA 02129, USA
    Hum Mol Genet 5:249-56. 1996
    ..These data confirm that TSC2 is indeed the relevant gene, and that a substantial number of sporadic cases arise from mutations in the TSC2 gene...
  41. ncbi request reprint Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34
    M van Slegtenhorst
    Department of Clinical Genetics, Erasmus University and University Hospital, Rotterdam, Netherlands
    Science 277:805-8. 1997
    ..In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor...
  42. ncbi request reprint Molecular genetic advances in tuberous sclerosis
    J P Cheadle
    Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK
    Hum Genet 107:97-114. 2000
    ..We also present the first comprehensive compilation and analysis of all reported TSC1 and TSC2 mutations, consider their diagnostic implications and review genotype/phenotype relationships...
  43. pmc Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome
    D J Kwiatkowski
    Hematology Oncology Unit, Massachusetts General Hospital, Charlestown 02129
    Am J Hum Genet 46:559-67. 1990
    ..Thus, single allelic deletion of the profilin locus may contribute to the clinical phenotype of the MDS in some patients but does not play a major role in the essential phenotype...
  44. ncbi request reprint Membrane ruffling, macropinocytosis and antigen presentation in the absence of gelsolin in murine dendritic cells
    M A West
    Department of Biochemistry, University of Dundee, Dundee, GB
    Eur J Immunol 29:3450-5. 1999
    ..Thus the major rearrangements of the actin cytoskeleton needed for DC antigen uptake and presentation can proceed in the absence of a major actin filament regulatory protein...
  45. pmc Neuroprotective effects of gelsolin during murine stroke
    M Endres
    Stroke and Neurovascular Regulation, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Clin Invest 103:347-54. 1999
    ..Hence, enhancement or mimicry of gelsolin activity may be neuroprotective during stroke...
  46. ncbi request reprint Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis
    S Kothakota
    Chiron Corporation, Emeryville, CA 94608, USA
    Science 278:294-8. 1997
    ..Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis...
  47. ncbi request reprint Human complement factor I: analysis of cDNA-derived primary structure and assignment of its gene to chromosome 4
    G Goldberger
    J Biol Chem 262:10065-71. 1987
    ..By exclusion, this defines as cellular the basis for the inefficient processing of pro-I by the HepG2 line. Chromosomal localization by the somatic cell hybrid method maps the factor I gene to chromosome 4...
  48. ncbi request reprint The mouse mammary gland requires the actin-binding protein gelsolin for proper ductal morphogenesis
    M R Crowley
    Division of Experimental Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA
    Dev Biol 225:407-23. 2000
    ..Our results provide the first evidence of an actin regulatory protein affecting mammary ductal growth through stromal-epithelial communication...
  49. pmc Profilin I is essential for cell survival and cell division in early mouse development
    W Witke
    European Molecular Biology Laboratory Monterotondo, Mouse Biology Program, Via Ramarini 32, 00016 Monterotondo, Italy
    Proc Natl Acad Sci U S A 98:3832-6. 2001
    ..Our results indicate that mouse profilin I is an essential protein that has dosage-dependent effects on cell division and survival during embryogenesis...
  50. ncbi request reprint COL5A1: fine genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos Syndrome type II
    D S Greenspan
    Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison 53706, USA
    Genomics 25:737-9. 1995
    ..This genetic mapping places COL5A1 between markers D9S66 and D9S67...
  51. ncbi request reprint Functional consequences of amyloidosis mutation for gelsolin polypeptide -- analysis of gelsolin-actin interaction and gelsolin processing in gelsolin knock-out fibroblasts
    H Kangas
    National Public Health Institute, Department of Human Molecular Genetics, Helsinki, Finland
    FEBS Lett 454:233-9. 1999
    ..These results suggest that, in patients with FAF, symptoms are caused by the accumulation in their tissues of amyloid derived from plasma gelsolin and are not due to functional differences in cytoplasmic gelsolin...