Georg Luebeck

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Fred Hutchinson Cancer Research Center
Public Health Sciences Division
Biostatistics and Biomathematics
Associate MemberAppointed: 2006
Professional Headshot of Georg Luebeck

Mailing Address

1100 Fairview Ave. N. M2-B500
Seattle, Washington 98109-1024
United States

Contact Information

Phone: (206) 667-4282
Fax: (206) 667-7004
gluebeck@fhcrc.org

Qualifications

Ph.D., University of Washington, Physics, 1986.
M.S., University of Washington, Physics, 1983.
Diplom in Physik (equiv. MS), University of Tuebingen, 1982.

Expertise and Research Interests

My main interest is in biomathematical descriptions of multistage carcinogenesis and their application to both experimental and epidemiological data. Research in this area is focused primarily on the two-stage clonal expansion (TSCE) model, a stochastic model based on Knudson's two-hit hypothesis, and multistage extensions thereof. A particular strength of this model is that it explicitly incorporates cell proliferation kinetics.

Some highlights of past activities: investigation of mathematical and statistical properties of the TSCE model hazard function (used to estimate age-specific cancer incidence and mortality), development of efficient algorithms for the computation of the hazard and survival function of the TSCE model for constant and piecewise constant parameters, exploration of parameter identifiability and stable reparameterizations for the TSCE model, extension of the model to more than two-stages, including tumor latency and detection.

These models have been successfully applied to various cancer data generating several interesting mechanistic hypotheses and predictions that can be interpreted in biological terms. Development of natural history models for cancers in colon, lung, and Barrett's esophagus, based on models that explicitly account for the multistage nature of carcinogenesis and cell proliferation, are underway. We expect these models to provide biologically better informed predictions for the efficacy of cancer screens, interventions, and preventions.

In addition to working with biologically-based models for the analysis of cancer endpoints, I am also interested in the development and application of stochastic models for the analysis of premalignant lesions such as altered hepatic lesions in rat or mouse liver (hepatocarcinogenesis) and benign neoplasms in colon and Barrett's esophagus.

Other Expertise

Much of the computer code we develop is in High Performance Fortran (HPF), which allows for parallelization of code on multiprocessor systems. We have set up two Beowulf clusters (the first at FHCRC!) running under Linux with dynamic load balancing using MOSIX. This configuration has been essential for the analysis of very large data sets.

I have extensive experience in scientific and statistical computing. My preferred programming environment for prototyping code and for statistical problems is R (a clone of S). I am author of the Bhat package, a set of tools written in F90 and R for the exploration of general likelihood functions (found at http://cran.r-project.org ).

Future Research

Computational and Theoretical Biology.

Topics of interest are:

Epigenetics and DNA Methylation. See our publication (in press) on the "Dynamics, Stability and Inheritance of somatic DNA Methylation Imprints."

Phylogenetics. In collaboration with Dr. Li Hsu (FHCRC), I have developed R-based software to explore SNP/LOH data and to construct maximum weight spanning trees based on Desper's algorithm. We are currently working on stochastic extensions of this approach.

Industrial Relevance

Our mathematical models of carcinogenesis are useful tools for biologically informed cancer risk prediction and quantitative risk assessment of environmental carcinogens.

Keywords

COS Keywords:

Breast Cancer, Cancer or Carcinogenesis, Colorectal Cancer, Lung Cancer, Mathematical Modeling, Mathematical Modeling (Medical), Physics, Prostate Cancer, Public Health, Radiation Oncology, Radiology.

Additional Terms:

Mathematical Modeling, Multistage Carcinogenesis, Radiation and Cancer.

Languages

(Reading, Writing, Speaking)

English: (Fluent, Fluent, Fluent)
German: (Fluent, Fluent, Fluent)
French: (Functional, Basic, Basic)

Previous Positions

2002-2006, Assistant Member, Fred Hutchinson Cancer Research Center, Public Health Sciences Division
1993-2002, Senior Staff Scientist, Fred Hutchinson Cancer Research Center, Public Health Sciences Division
1988-1993, Staff Scientist, Fred Hutchinson Cancer Research Center, Public Health Sciences Division
1986-1988, Postdoctoral Fellow, Niels Bohr Institut, Copenhagen

Publications

  • Sontag LB, Lorincz MC and Luebeck EG (2006) Dynamics, Stability and Inheritance of somatic DNA Methylation Imprints, Journal of Theoretical Biology, In Press
  • Meza R, Luebeck EG, Moolgavkar SH (Oct 2005) Gestational mutations and carcinogenesis., Mathematical Biosciences, 197 (2), 188-210 Abstract
  • Dewanji A, Luebeck EG, Moolgavkar SH (Oct 2005) A generalized Luria-Delbruck model., Mathematical Biosciences, 197 (2), 140-52 Abstract
  • Luebeck EG, Buchmann A, Schneider D, Moolgavkar SH, Schwarz M (Feb 2005) Modulation of liver tumorigenesis in Connexin32-deficient mouse., Mutation Research, 570 (1), 33-47 Abstract
  • Heidenreich WF, Luebeck EG, Hazelton WD, Paretzke HG, Moolgavkar SH, Response to the commentary of Donald A. Pierce (Radiat. Res. 160, 718-723, 2003)., Radiation Research, 161(3), 369-70; author reply, Mar 2004 Abstract
  • Curtis SB, Hazelton WD, Luebeck EG, Moolgavkar SH (2004) From mechanisms to risk estimation--bridging the chasm., Advances in Space Research : the Official Journal of the Committee On Space Research (cospar)., 34 (6), 1404-9 Abstract
  • Heidenreich WF, Luebeck EG, Moolgavkar SH (Jan 2004) Effects of exposure uncertainties in the TSCE model and application to the Colorado miners data., Radiation Research, 161 (1), 72-81 Abstract
  • Moolgavkar SH, Luebeck EG (Dec 2003) Multistage carcinogenesis and the incidence of human cancer., Genes, Chromosomes & Cancer, 38 (4), 302-6 Abstract
  • de Gunst MC, Dewanji A, Luebeck EG (May 2003) Exploring heterogeneity in tumour data using Markov chain Monte Carlo., Statistics in Medicine, 22 (10), 1691-707 Abstract
  • Heidenreich WF, Luebeck EG, Hazelton WD, Paretzke HG, Moolgavkar SH (Nov 2002) Multistage models and the incidence of cancer in the cohort of atomic bomb survivors., Radiation Research, 158 (5), 607-14 Abstract
  • Luebeck EG, Moolgavkar SH (Nov 2002) Multistage carcinogenesis and the incidence of colorectal cancer., Proceedings of the National Academy of Sciences of the United States of America., 99 (23), 15095-100 Abstract
  • Luebeck EG, Hazelton WD (Sep 2002) Multistage carcinogenesis and radiation., Journal of Radiological Protection : Official Journal of the Society for Radiological Protection., 22 (3A), A43-9 Abstract
  • Gregori G, Hanin L, Luebeck G, Moolgavkar S, Yakovlev A, Testing goodness of fit for stochastic models of carcinogenesis, Mathematical Biosciences, 175(1), 13-29, January 2002 Abstract
  • Curtis SB, Luebeck EG, Hazelton WD, Moolgavkar SH (2002) A new perspective of carcinogenesis from protracted high-LET radiation arises from the two-stage clonal expansion model., Advances in Space Research : the Official Journal of the Committee On Space Research (cospar)., 30 (4), 937-44 Abstract
  • Hazelton WD, Luebeck EG, Heidenreich WF, Moolgavkar SH (Jul 2001) Analysis of a historical cohort of Chinese tin miners with arsenic, radon, cigarette smoke, and pipe smoke exposures using the biologically based two-stage clonal expansion model., Radiation Research, 156 (1), 78-94 Abstract
  • Moolgavkar SH, Turim J, Brown RC, Luebeck EG (Apr 2001) Long man-made fibers and lung cancer risk., Regulatory Toxicology and Pharmacology : Rtp, 33 (2), 138-46 Abstract
  • Curtis SB, Luebeck EG, Hazelton WD, Moolgavkar SH (2001) The role of promotion in carcinogenesis from protracted high-LET exposure., Physica Medica : Pm : an International Journal Devoted to the Applications of Physics to Medicine and Biology : Official Journal of the Italian Association of Biomedical Physics (aifb)., 17 Suppl 1, 157-60 Abstract
  • Luebeck EG, Curtis SB, Hazelton WD, Moolgavkar SH (Dec 2000) The importance of promotion in lung carcinogenesis for protracted exposures to radon and radon progeny., Radiation Research, 154 (6), 730;discussion 730-1 Abstract
  • Luebeck EG (Nov 2000) From cyclophosphamide hematotoxicity to modeling cancer., Journal of Toxicology and Environmental Health. Part a, 61 (5-6), 515-20 Abstract
  • Luebeck EG, Buchmann A, Stinchcombe S, Moolgavkar SH, Schwarz M (Aug 2000) Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on initiation and promotion of GST-P-positive foci in rat liver: A quantitative analysis of experimental data using a stochastic model., Toxicology and Applied Pharmacology, 167 (1), 63-73 Abstract
  • Grasl-Kraupp B, Luebeck G, Wagner A, Low-Baselli A, de Gunst M, Waldhor T, Moolgavkar S, Schulte-Hermann R, Quantitative analysis of tumor initiation in rat liver: role of cell replication and cell death (apoptosis), Carcinogenesis, 21(7), 1411-21, July 2000 Abstract
  • Moolgavkar SH, Luebeck EG, Turim J, Brown RC (Feb 2000) Lung cancer risk associated with exposure to man-made fibers., Drug and Chemical Toxicology, 23 (1), 223-42 Abstract
  • Luebeck EG, Heidenreich WF, Hazelton WD, Paretzke HG, Moolgavkar SH, Biologically based analysis of the data for the Colorado uranium miners cohort: age, dose and dose-rate effects, Radiation Research, 152(4), 339-51, October 1999 Abstract
  • de Gunst MC, Luebeck EG, A method for parametric estimation of the number and size distribution of cell clusters from observations in a section plane, Biometrics, 54(1), 100-12, March 1998 Abstract
  • Kai M, Luebeck EG, Moolgavkar SH, Analysis of the incidence of solid cancer among atomic bomb survivors using a two-stage model of carcinogenesis, Radiation Research, 148(4), 348-58, October 1997 Abstract
  • Heidenreich WF, Luebeck EG, Moolgavkar SH, Some properties of the hazard function of the two-mutation clonal expansion model, Risk Analysis, 17(3), 391-9, June 1997 Abstract
  • Luebeck EG, Moolgavkar SH, Biologically based cancer modeling, Drug and Chemical Toxicology, 19(3), 221-43, August 1996 Abstract
  • Dewanji A, Luebeck EG, Moolgavkar SH, A biologically based model for the analysis of premalignant foci of arbitrary shape, Mathematical Biosciences, 135(1), 55-68, 1996 Abstract
  • Moolgavkar SH, Luebeck EG, Buchmann A, Bock KW, Quantitative analysis of enzyme-altered liver foci in rats initiated with diethylnitrosamine and promoted with 2,3,7,8-tetrachlorodibenzo-p-dioxin or 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, Toxicology and Applied Pharmacology, 138(1), 31-42, May 1996 Abstract
  • Luebeck EG, Curtis SB, Cross FT, Moolgavkar SH, Two-stage model of radon-induced malignant lung tumors in rats: effects of cell killing, Radiation Research, 145(2), 163-73, February 1996 Abstract
  • Luebeck EG, Grasl-Kraupp B, Timmermann-Trosiener I, Bursch W, Schulte-Hermann R, Moolgavkar SH, Growth kinetics of enzyme-altered liver foci in rats treated with phenobarbital or alpha-hexachlorocyclohexane, Toxicology and Applied Pharmacology, 130(2), 304-15, February 1995 Abstract
  • Luebeck EG, Moolgavkar SH, Simulating the process of malignant transformation, Mathematical Biosciences, 123(2), 127-46, October 1994 Abstract
  • De Gunst MC, Luebeck EG, Quantitative analysis of two-dimensional observations of premalignant clones in the presence or absence of malignant tumors, Mathematical Biosciences, 119(1), 5-34, January 1994 Abstract
  • Moolgavkar SH, Luebeck EG, Interpretation of labeling indices in the presence of cell death, Carcinogenesis, 13(6), 1007-10, June 1992 Abstract
  • Moolgavkar SH, Luebeck EG, Multistage carcinogenesis: population-based model for colon cancer, Journal of the National Cancer Institute, 84(8), 610-8, 1992 Abstract
  • Luebeck EG, Moolgavkar SH, Buchmann A, Schwarz M, Effects of polychlorinated biphenyls in rat liver: quantitative analysis of enzyme-altered foci, Toxicology and Applied Pharmacology, 111(3), 469-84, December 1991 Abstract
  • Dewanji A, Moolgavkar SH, Luebeck EG, Two-mutation model for carcinogenesis: joint analysis of premalignant and malignant lesions, Mathematical Biosciences, 104(1), 97-109, April 1991 Abstract
  • Luebeck EG, Moolgavkar SH, Stochastic analysis of intermediate lesions in carcinogenesis experiments, Risk Analysis, 11(1), 149-57, March 1991 Abstract
  • Moolgavkar SH, Luebeck EG, de Gunst M, Port RE, Schwarz M, Quantitative analysis of enzyme-altered foci in rat hepatocarcinogenesis experiments--I. Single agent regimen, Carcinogenesis, 11(8), 1271-8, August 1990 Abstract

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