Lynn Hlatky, PhD
Director
Center of Cancer Systems Biology
Email: hlatky [at] cancer-systems-biology.org
Lynn Hlatky is the founding director of the Center of Cancer Systems Biology. Prior to founding the Center, she was at Dana-Farber Cancer Institute and in the Department of Radiation Oncology at Harvard Medical School. The mission of the Center of Cancer Systems Biology (CCSB) is based on the appreciation that carcinogenesis evolves at multiple levels ranging from molecular signalings to cellular and tissue interactions, and that only by their concerted study can the entire process be understood and translated into advances in clinical treatment and the development of novel therapies. Accordingly, the CCSB incorporates researchers with expertise in clinical oncology, cancer biology, molecular biology, radiobiology, bioengineering, mathematics, physics and engineering, chemistry, and computational biology.
Dr. Hlatky has also directed three major federal program grants
from different national agencies:
- From the National Cancer Institute (NCI), Dr. Hlatky is the
principal investigator of one of twelve inter-disciplinary Centers
for Cancer Systems Biology under the
NCI's
Integrative Cancer Biology Program. This collaborative network
focuses on the analysis of cancer as a complex biological system.
Under this program, our efforts augment the current understanding
of carcinogenesis and identify how the tumor cell's environment
affects disease development and progression. This work involves
collaboration with researchers at NYU Langone Medical Center; at
the University of California, Berkeley; and at Lawrence Berkeley
National Laboratory.
- As a designated
NASA Specialized Center of Research (NSCOR), our CCSB
contributed investigations into radiation-induced carcinogenesis to
the multi-institutional mission. Our program involved investigators
at University of California, Berkeley and at University of
Heidelberg, Germany.
- Through the Low-Dose Radiation Research Program of the U.S. Department of Energy (DOE), the CCSB investigated the relationship between biological responses to low-dose radiation and health consequences.
In addition, CCSB investigators have collaborated with
Dr. Ingolf Tuerk on a translational prostate
cancer study, the goal of which is to improve understanding of the
characteristics that distinguish different stages of prostate
cancer and associated patient prognosis.
Research Interests:
- Carcinogenesis and tumor growth dynamics
- Radiobiology
- Translational studies on microenvironmental influence
- DNA damage and repair
- Tumor angiogenesis
- Tumor–cell fusion
Recent Publications:
(click on title to go to manuscript abstract)
- Oh J, Hlatky L, Jeong YS, Kim D. Therapeutic
Effectiveness of Anticancer Phytochemicals on Cancer Stem Cells.
Toxins (Basel). 2016 Jun 30;8(7). PMCID: PMC4963832. [Open Access]
- Gao X, Sishc BJ, Nelson CB, Hahnfeldt P, Bailey SM, Hlatky
L. Radiation-Induced Reprogramming of Pre-Senescent Mammary
Epithelial Cells Enriches Putative CD44(+)/CD24(-/low) Stem Cell
Phenotype. Front Oncol. 2016 Jun 14;6:138. PMCID: PMC4905979. [Open Access]
- Ravi D, Beheshti A, Abermil N, Passero F, Sharma J, Coyle M,
Kritharis A, Kandela I, Hlatky L, Sitkovsky MV, Mazar A,
Gartenhaus RB, Evens AM.Proteasomal Inhibition by Ixazomib Induces
CHK1 and MYC-Dependent Cell Death in T-cell and Hodgkin Lymphoma.
Cancer Res. 2016 Jun 1;76(11):3319-31. Epub
2016 Mar 17.
- Sridharan DM, Asaithamby A, Blattnig SR, Costes SV, Doetsch
PW, Dynan WS, Hahnfeldt P, Hlatky L, Kidane Y,
Kronenberg A, Naidu MD, Peterson LE, Plante I, Ponomarev AL,
Saha J, Snijders AM, Srinivasan K, Tang J, Werner E, Pluth JM. Evaluating biomarkers to model cancer risk post cosmic ray
exposure.
Life Sci Space Res (Amst). 2016 Jun;9:19-47. Epub 2016 May 21. [Open
Access]
- Benzekry S, Beheshti A, Hahnfeldt P, Hlatky
L. Capturing the driving role of tumor-host crosstalk in a
dynamical model of tumor growth. Bio Protocol. 2015 Nov
5;5(21). PMCID: PMC4957653. [Open Access]
- Beheshti A, Wage J, McDonald JT, Lamont C, Peluso M, Hahnfeldt
P, Hlatky L. Tumor-host signaling interaction reveals a
systemic, age-dependent splenic immune influence on tumor
development. Oncotarget. 2015 Nov 3;6(34):35419-32. Epub 2015
Oct 21. PMCID: PMC4742115. [Open Access]
- Wage J, Ma L, Peluso M, Lamont C, Evens AM, Hahnfeldt P,
Hlatky L, Beheshti A. Proton irradiation impacts age-driven modulations
of cancer progression influenced by immune system transcriptome
modifications from splenic tissue. J Radiat Res. 2015
Sep;56(5):792-803. Epub 2015 Aug 7. PMCID: PMC4577010. [Open
Access]
- Girdhani S, Sachs R, Hlatky L. Biological effects of proton radiation: an
update. Radiat Prot Dosimetry. 2015 Sep;166(1-4):334-8. Epub
2015 Apr 20.
- Suresh Kumar MA, Peluso M, Chaudhary P, Dhawan J, Beheshti
A, Manickam K, Thapar U, Pena L, Natarajan M, Hlatky
L, Demple B, Naidu M. Fractionated radiation exposure of rat
spinal cords leads to latent neuro-inflammation in brain,
cognitive deficits, and alterations in Apurinic
Endonuclease 1. PLoS One. 2015 Jul
24;10(7):e0133016. PMCID: PMC4514622. [Open Access]
- Barcellos-Hoff MH, Blakely EA, Burma S, Fornace AJ
Jr, Gerson S, Hlatky L, Kirsch DG, Lederer U, Shay
J, Wang Y, Weil MM. Concepts and challenges in cancer risk
prediction for the space radiation environment. Life Sci
Space Res (Amst). 2015 Jul;6:92-103. Epub 2015 Jul
17. [Open Access]
- Beheshti A, Benzekry S, McDonald JT, Ma L, Peluso M,
Hahnfeldt P, Hlatky L. Host age is a systemic regulator of gene
expression impacting cancer progression. Cancer Res. 2014 Mar
15;75(6):1134-43. Epub 2015 Mar 2. PMCID: PMC4397972. [Open Access]
- Radivoyevitch T, Siranart N, Hlatky L, Sachs R. Stochastic process pharmacodynamics: dose timing
in neonatal gentamicin therapy as an example. AAPS J. 2015
Mar;17(2):447-56. Epub 2015 Feb 7. PMCID: PMC4365091. [Open Access]
- Nguyen DH, Ouyang H, Mao JH, Hlatky L, Barcellos-Hoff
MH. Distinct luminal-type mammary carcinomas arise
from orthotopic Trp53-null mammary transplantation of juvenile
versus adult mice. Cancer Res. 2014 Dec
1;74(23):7149-58. Epub 2014 Oct 3. PMCID: PMC4252877. [Open Access]
- Gale RP, Hlatky L, Radivoyevitch T, Sachs RK. Why is there so much therapy-related AML and
MDS and so little therapy-related CML? Leuk Res. 2014
Oct;38(10);1162-4. Epub 2014 Aug
11.
- Benzekry S, Lamont C, Beheshti A, Tracz A, Ebos JM,
Hlatky L, Hahnfeldt P. Classical mathematical models for
description and prediction of experimental tumor
growth. PLOS Comput Biol. 2014 Aug
28;10(8).e1003800. eCollection 2014. PMCID: PMC4148196. [Open Access]
- Weekes SL, Barker B, Bober S, Cisneros K, Cline J,
Thompson A, Hlatky L, Hahnfeldt P, Enderling H. A
multicompartment mathematical model of cancer stem cell-driven
tumor growth dynamics. Bull Math Biol. 2014
Jul;76(7):1762-82. Epub 2014 May 20. PMCID:
PMC4140966.
- Gao X, McDonald JT, Naidu M, Hahnfeldt P, Hlatky
L. A
proposed quantitative index for assessing the potential
contribution of reprogramming to cancer stem cell kinetics. Stem
Cells Int. 2014;2014:249309. Epub 2014
May 12. PMCID: PMC4052692. [Open Access]
- Batra JS, Girdhani S, Hlatky L. A quest to identify prostate cancer circulating
biomarkers with a bench-to-bedside potential. J
Biomarkers. 2014 Mar 12;2014:321680. Epub 2014
Jan 10. PMCID: PMC4437363. [Open Access]
- Girdhani S, Lamont C, Peluso M, Sun M, Hlatky
L. 56Fe ion irradiation enhances angiogenesis and
other inter-cellular determinants of carcinogenesis risk. J
Radiat Res. 2014 Mar 1;55 Suppl
1:i124-i126. PMCID: PMC3941549. [Open
Access]
- Beheshti A, Peluso M, Lamont C, Hahnfeldt P, Hlatky
L. Proton irradiation augments the suppression of
tumor progression observed with advanced age. Radiat
Res. 2014 Mar;181(3):272-83. Epub 2014 Feb 25. COVER ARTICLE
- McDonald JT, Briggs C, Szelag H, Peluso M, Schneider D,
Perepletchikov A, Klement GL, Tuerk I, Hlatky
L. Chronic low dose-rate radiation down-regulates
transcription related to mitosis and chromosomal movement
similar to acute high dose in prostate cells. Int J Radiat
Biol. 2014 Mar;90(3):231-40. Epub 2014 Jan 8.
- Piccioni A, Gaetani E, Neri V, Gatto I, Palladino M,
Silver M, Smith RC, Giarretta I, Pola E, Hlatky L, Pola
R. Sonic hedgehog therapy in a mouse model of age-associated
impairment of skeletal muscle regeneration. J Gerontol A
Biol Sci Med Sci. 2014 Mar;69(3):245-52. Epub 2013 Jun 18. PMCID: PMC3976139. [Open Access] EDITOR'S CHOICE selection
- Radivoyevitch T, Jankovic GM, Tiu RV, Saunthararajah Y, Jackson
RC, Hlatky LR, Gale RP, Sachs RK. Sex differences in the incidence of chronic myeloid
leukemia. Radiat Environ Biophys. 2014 Mar;53(1):55-63. Epub
2013 Dec 13. PMCID: PMC3943788.
- Hlatky L, Hahnfeldt P. Beyond the cancer cell:
progression-level determinants highlight the multi-scale nature of
carcinogenesis risk. Cancer Res. 2014 Feb 1;74(3):659-64. Epub
2013 Nov 22. [Open Access]
- Rietman EA, Hahnfeldt P, Hlatky L. A Review
and Perspective on Thermodynamics Applied to Molecular Systems
and Cancer Biology. In: Valente AX, Sarkar A, Gao Y (eds). Recent Advances in Systems Biology
Research. Nova Science Publishers, Inc., 2014:49-78. In
Series: Systems Biology — Theory, Techniques and
Applications.
- Fakir H, Hlatky L, Li H, Sachs R. Repopulation of interacting tumor cells during fractionated
radiotherapy: Stochastic modeling of the tumor control
probability. Med
Phys. 2013 Dec;40(12):121716. Epub 2013 Nov 15. PMCID:
PMC384375. [Open Access] EDITOR'S PICKS selection
- Palladino M, Gatto I, Neri V, Straino S, Smith RC, Silver
M, Gaetani E, Marcantoni M, Giarretta I, Stigliano E, Capogrossi
M, Hlatky L, Landolfi R, Pola R. Angiogenic impairment of the vascular endothelium: a
novel mechanism and potential therapeutic target in muscular
dystrophy. Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2867-76. Epub 2013 Sep 26. [Open Access]
- Beheshti A, Pinzer BR, McDonald JT, Stampanoni M,
Hlatky L. Early tumor development captured through
nondestructive, high resolution differential phase contrast
X-ray imaging. Radiat Res. 2013 Nov;180(5):448-54. Epub 2013
Oct 14. PMCID: PMC3925470.
- Wang Y, Zhou TH, Zhi Z, Barakat A, Hlatky L, Querfurth
H. Multiple effects of β-amyloid on single
excitatory synaptic connections in the PFC. Front Cell
Neurosci. 2013 Sep 3;7:129. PMCID: PMC3759796. [Open Access]
- Almog N, Briggs C, Beheshti A, Ma L, Wilkie KP, Rietman E,
Hlatky L. Transcriptional changes induced by the tumor
dormancy-associated microRNA-190. Transcription. 2013 Jul
1;4(4). PMCID: PMC3977918. [Open Access] COVER ARTICLE
- Rietman EA, Friesen DE, Hahnfeldt P, Gatenby R, Hlatky
L, Tuszynski JA. An integrated multidisciplinary model
describing initiation of cancer and the Warburg
hypothesis. Theor Biol Med Model. 2013 Jun
10;10(1):39. PMCID: PMC3689044. [Open Access]
- Hahnfeldt P, Hlatky L, Klement GL. Center of Cancer
Systems Biology second annual workshop—tumor metronomics:
timing and dose level dynamics. Cancer Res. 2013 May
15;73(10):2949-54. Epub 2013 Mar 14. PMCID: PMC3696500. [Open Access]
- Enderling H, Hlatky L, Hahnfeldt P. Cancer stem cells: a minor cancer subpopulation
that redefines global cancer features. Front Oncol. 2013 Apr
15;3:76. Epub 2013 Apr 15. PMCID: PMC3625721. [Open Access]
- Gao X, McDonald JT, Hlatky L, Enderling
H. Acute and fractionated irradiation differentially modulate glioma
stem cell division kinetics. Cancer Res. 2013 Mar
1;73(5):1481-90. Epub 2012 Dec 26. PMCID: PMC3594421. [Open Access]
- Girdhani S, Sachs R, Hlatky L. Biological effects of
proton radiation: what we know and don't know. Radiat Res. 2013
Mar;179(3):257-72. Epub 2013 Feb 1. COVER ARTICLE
- Beheshti A, Sachs RK, Peluso
M, Rietman E, Hahnfeldt P, Hlatky L. Age and space irradiation modulate tumor progression:
implications for carcinogenesis risk. Radiat Res. 2013 Feb;179(2):208-20. Epub 2013 Jan 4.
- Rietman EA, McDonald JT, Hlatky L. Organism mutation
stability and cancer. In: Shoja MM, Agutter PS, Tubbs RS, Ghanei M,
Ghabili K, Harris A, Loukas M (eds). Hypotheses
in Clinical Medicine. Nova Science Publishers, Inc.,
2013:135-46.
- Enderling H, Almog N, Hlatky L, editors. Systems Biology of Tumor Dormancy. New
York: Springer, 2013: 291p. In Series: Advances in Experimental
Medicine and Biology, Vol. 734.
- Gao X, McDonald JT, Hlatky L, Enderling
H. Cell-Cell Interactions in Solid Tumors — the Role of Cancer
Stem Cells. In: D'Onofrio A, Cerrai P, Gandolfi A (eds). New Challenges for Cancer Systems
Biomedicine. Milan, Italy: Springer, 2012:191-204. In
Series: SIMAI Springer Series: Bellomo N, Formaggia L, Bangerth W,
Nobile F, Pareschi L, Tercero PP, Tosin A, Zubelli JP (series eds).
- Sasi SP, Yan X, Enderling H, Park D, Gilbert HY, Curry C,
Coleman C, Hlatky L, Qin G, Kishore R, Goukassian
DA. Breaking the ‘harmony’ of TNF-α signaling
for cancer treatment. Oncogene. 2012 Sep
13;31(37):4117-27. Epub 2011 Dec 12. PMCID: PMC3962797. [Open Access]
- Satchi-Fainaro R, Ferber S, Segal E, Ma L, Dixit N, Ijaz
A, Hlatky L, Abdollahi A, Almog N. Prospective
identification of glioblastoma cells generating dormant
tumors. PLoS One. 2012;7(9):e44395. Epub 2012 Sep
6. PMCID: PMC3435314. [Open Access]
- Almog N, Ma L, Schwager C, Brinkmann BG, Beheshti A,
Vajkoczy P, Folkman J, Hlatky L, Abdollahi A. Consensus micro RNAs governing the switch of
dormant tumors to the fast-growing angiogenic
phenotype. PLoS One. 2012;7(8):e44001. Epub 2012
Aug 31. PMCID: PMC3432069. [Open Access]
- Palladino M, Gatto I, Neri V, Stigliano E, Smith RC, Pola E,
Straino S, Gaetani E, Capogrossi M, Leone G, Hlatky L,
Pola R. Combined therapy with sonic hedgehog gene transfer and
bone marrow-derived endothelial progenitor cells enhances
angiogenesis and myogenesis in the ischemic skeletal muscle. J
Vasc Res. 2012;49(5):425-31. Epub 2012 Jun 22. [Open Access]
- Enderling H, Hlatky L, Hahnfeldt P. Immunoediting:
evidence of the multifaceted role of the immune system in
self-metastatic tumor growth. Theor Biol Med Model. 2012 Jul
28;9:31. Epub 2012 Jul 28. PMCID: PMC3499182. [Open Access]
- Girdhani S, Lamont C, Hahnfeldt P, Abdollahi A, Hlatky
L. Proton irradiation suppresses angiogenic genes and
impairs cell invasion and tumor growth. Radiat Res. 2012
Jul;178(1):33-45. Epub 2012 Jun 14.
- Breitkreutz D, Hlatky L, Rietman E, Tuszynski
JA. Molecular signaling network complexity is correlated with
cancer patient survivability. Proc Natl Acad Sci U S A. 2012
Jun 5;109(23):9209-12. Epub 2012 May 21. PMCID: PMC3384193. [Open Access]
- Klement GL, Goukassian D, Hlatky L, Carrozza J,
Morgan JP, Yan X. Cancer Therapy Targeting the HER2-PI3K
Pathway: Potential Impact on the Heart. Front
Pharmacol. 2012 Jun 27;3:113. Epub 2012 Jun 27. PMCID:
PMC3384262. [Open Access]
- Sharungbam GD, Schwager C, Chiblak S, Brons S, Hlatky
L, Haberer T, Debus J, Abdollahi A. Identification of stable
endogenous control genes for transcriptional profiling of
photon, proton and carbon-ion irradiated cells. Radiat
Oncol. 2012 May 17;7:70. PMCID: PMC3422209. [Open Access]
- Radivoyevitch T, Hlatky L, Landaw J, Sachs
RK. Quantitative modeling of chronic myeloid leukemia: insights
from radiobiology. Blood. 2012 May 10;119(19):4363-71. Epub
2012 Feb 21. PMCID: PMC3362357. [Open Access] COVER ARTICLE
- Enderling H, Hahnfeldt P, Hlatky L, Almog
N. Systems biology of tumor dormancy:
linking biology and mathematics on multiple scales to improve
cancer therapy. Cancer Res. 2012 May 1;72(9):2172-5. Epub
2012 Mar 13. PMCID: PMC3374524. [Open Access]
- Enderling H, Hlatky L, Hahnfeldt P. The promoting role of a tumour-secreted
chemorepellent in self-metastatic tumour progression. Math
Med Biol. 2012 Mar;29(1):21-9. Epub 2010 Oct 6.
- Hlatky L. Double-strand break motions shift
radiation risk notions? Proc Natl Acad Sci U S A. 2012 Jan
10;109(2):351-2. Epub 2011 Dec 30. PMCID: PMC3258590. [Open Access]
- Morton CI, Hlatky L, Hahnfeldt P, Enderling
H. Non-stem cancer cell kinetics modulate solid tumor
progression. Theor Biol Med Model. 2011 Dec 30;8:48. PMCID:
PMC3285090. [Open Access]
- Javaherian K, Lee TY, Tjin Tham Sjin RM, Parris GE,
Hlatky L. Two endogenous antiangiogenic inhibitors,
endostatin and angiostatin, demonstrate biphasic curves in their
antitumor profiles. Dose Response. 2011;9(3):369-76. Epub 2010 Oct 21. PMCID: PMC3186931. [Open Access]
- Domhan S, Ma L, Tai A, Anaya Z, Beheshti A, Zeier M,
Hlatky L, Abdollahi A. Intercellular communication by
exchange of cytoplasmic material via tunneling nano-tube like
structures in primary human renal epithelial cells. PLoS
One. 2011;6(6):e21283. Epub 2011 Jun 27. PMCID:
PMC3124493. [Open Access]
- Sachs RK, Johnsson K, Hahnfeldt P, Luo J, Chen A,
Hlatky L. A multicellular basis for the origination of
blast crisis in chronic myeloid leukemia. Cancer Res. 2011
Apr 15;71(8):2838-47. Epub 2011 Apr 12. PMCID: PMC3537493. [Open Access]
- Barcellos-Hoff MH, Brenner DJ, Brooks LA, Formenti S,
Hlatky L, Locke PA, Shore R, Tenforde T, Travis EL,
Williams J. Low-dose radiation
knowledge worth the cost. Science. 2011 Apr
15;332(6027):305-6.
- McDonald JT, Kim K, Norris AJ, Vlashi E, Phillips TM,
Lagadec C, Della Donna L, Ratikan J, Szelag H, Hlatky
L, McBride WH. Ionizing radiation activates the Nrf2
antioxidant response. Cancer Res. 2010 Nov1;70(21):8886-95. Epub 2010
Oct 12. PMCID: PMC2970706. [Open Access]
- Liangos O, Domhan S, Schwager C, Zeier M, Huber PE,
Addabbo F, Goligorsky MS, Hlatky L, Jaber BL, Abdollahi
A. Whole blood transcriptomics in cardiac surgery identifies a
gene regulatory network connecting ischemia reperfusion with
systemic inflammation. PLoS One. 2010 Oct
27;5(10):e13658. PMCID: PMC2965092. [Open Access]
- Enderling H, Hlatky L, Hahnfeldt P. Tumor
morphological evolution: directed migration and gain and loss
of the self-metastatic phenotype. Biol Direct. 2010 Apr 20;5:23. PMCID: PMC2868833. [Open Access]
- Sachs RK, Hlatky L. A rapid-mutation approximation
for cell population dynamics. Bull Math Biol. 2010
Feb;72(2):359-74. Epub 2009 Dec 30. [Open Access]
- Enderling H, Anderson AR, Chaplain MA, Beheshti A, Hlatky
L, Hahnfeldt P. Paradoxical dependencies of tumor dormancy
and progression on basic cell kinetics. Cancer Res. 2009
Nov 15;69(22):8814-21. Epub 2009 Nov 3. [Open Access]
- Fakir H, Tan WY, Hlatky L, Hahnfeldt P, Sachs
RK. Stochastic population dynamic effects for lung cancer
progression. Radiat Res. 2009 Sep;172(3):383-93.
- Shuryak I, Hahnfeldt P, Hlatky L, Sachs RK, Brenner
DJ. A new view of radiation-induced cancer: integrating short-
and long-term processes. Part I: approach. Radiat Environ
Biophys. 2009 Aug;48(3):263-74. Epub 2009 Jun
18. PMCID: PMC2714893. [Open Access]
- Shuryak I, Hahnfeldt P, Hlatky L, Sachs RK, Brenner
DJ. A new view of radiation-induced cancer: integrating short-
and long-term processes. Part II: second cancer risk
estimation. Radiat Environ Biophys. 2009
Aug;48(3):275-86. Epub 2009 Jun 5. PMCID: PMC2714894. [Open Access]
- Enderling H, Hlatky L, Hahnfeldt P. Migration
rules: tumours are conglomerates of self-metastases. Br J
Cancer. 2009 Jun 16;100(12):1917-25. Epub 2009 May
19. PMCID: PMC2714240. [Open Access]
- Almog N, Ma L, Raychowdhury R, Schwager C, Erber R, Short
S, Hlatky L, Vajkoczy P, Huber PE, Folkman J, Abdollahi
A. Transcriptional switch of dormant tumors to fast-growing
angiogenic phenotype. Cancer Res. 2009 Feb
1;69(3):836-44. Epub 2009 Jan 27. [Open Access] COVER ARTICLE
- Enderling H, Park D, Hlatky L, Hahnfeldt P. The
importance of spatial distribution of stemness and
proliferation state in determining tumor radioresponse. Math
Model Nat Phenom. 2009 Jan;4(03):117-33.