||Yang Liu, Ph.D.
Professor, Department of Medicine,
of Gastroenterology, Hepatology and Nutrition
Associate Professor, Department of Bioengineering
Director, Biomedical Optical Imaging Laboratory (BOIL)
University of Pittsburgh, University of Pittsburgh Cancer Institute
Hillman Cancer Center 2.32
5117 Centre Ave
B.S., Chemistry, Nankai University, China, 1999
M.S., Chemistry, The University of Chicago, Chicago, IL, 2002
Ph.D., Biomedical Engineering (Biomedical Optics), Northwestern
University, Evanston, IL, 2006
Other Professional Experience
Johnson & Johnson, Skillman, NJ
Johnson & Johnson, Skillman, NJ
The laboratory of Dr. Yang Liu integrates multi-disciplinary approaches spanning engineering, optics, physics, chemistry and biology and develops imaging technologies to address important clinical dilemma of how to better predict the individual's cancer progression risk in a large number of at-risk population, and how to improve the diagnostic accuracy of malignancy. Early cancer detection currently relies on screening the entire at-risk population, as with colonoscopy and mammography. Frequent, invasive surveillance of patients at risk for developing cancer carries financial, physical, and emotional burdens because clinicians lack tools to accurately predict which patients will actually progress into malignancy. Current clinical gold standard for diagnosing cancer and predicting cancer progression risk relies on the evaluation of nuclear morphology by a trained pathologist using bright-field microscope, which limits the assessment of nuclear architecture to microscale with very limited performance on a personalized level, especially in patients without the presence of clinically significant lesions such as patients with ulcerative colitis or atypical hyperplasia in breast.
To address these highly unmet clinical need, our group aims for both technology development and mechanistic understanding of cancer biology. First, given that nuclear architecture plays an important role in regulating the function of genome and epigenome in cancer progression, does the genome-level high-order nuclear architecture at nanoscale provide earlier and more accurate prediction of cancer progression? Second, if it does, can we develop clinically applicable instrument to interrogate nanoscale nuclear architecture with a high throughput to better inform the clinical decision-making?
We are working with a large multidisciplinary team that encompasses expertise in bioengineering, physics, electrical engineering, chemistry, cancer biology, pathology, oncology, gastroenterology and surgery at University of Pittsburgh and University of Pittsburgh Medical Center (UPMC). The main goal of our research is to translate bench-top imaging technologies into clinical practice and improve patient care.
Our group focuses on the following projects:
- Development of a clinically applicable imaging technology for high-throughput nanoscale nuclear architecture mapping (nanoNAM) of clinical tissue samples.
- Clinical application to predict early-cancer progression in inflammatory bowel disease and breast pre-cancerous lesions and improve cancer diagnosis.
- Clinical application of nanoNAM and quantitative phase imaging to improve the diagnostic accuracy of cytology (e.g., urine and cervix).
- Super-resolution imaging of genome organization at a single nucleosome level (or "nucleome") in cancer progression.
- Development of 3D super-resolution fluorescence nanoscopy for imaging thick tissue.
Selected Recent Publications
- Uttam S, Liu Y. Fourier phase in Fourier-domain optical coherence tomography. Journal of Optical Society of America A, 2015; 32(12): 2286-2306. Link
- [Uttam S*, Pham HV*], LaFace J, Leibowitz B, Yu J, Brand RE, Hartman DJ, Liu Y. Early prediction of cancer progression by depth-resolved nanoscale maps of nuclear architecture from unstained tissue specimens. Cancer Research, 2015; 75(22): 4718-4727. (* Co-first authors) Link
- Ma H, Xu J, Jin J, Gao Y, Lan L, Liu Y. Fast and precise 3D fluorophore localization based on gradient fitting. Scientific Reports, 2015; 5: 14335. ArticleLink CodeLink
- Sun L, Tan R, Xu J, LaFace J, Gao Y, Xiao, Y, Attar, M, Neumann C, Li G-M; Su B, Liu Y, Levine A, Nakajima S, Lan L. Targeted DNA damage at individual telomeres disrupts their integrity and triggers cell death, Nucleic Acids Research 2015; 43: 6334-6347. Link
- Del Portillo A, Lagana SM, Yao Y, Uehara T, Jhala N, Ganguly T, Nagy P, Gutierrez J, Luna A, Abrams J, Liu Y, Brand R, Sepulveda JL, Falk GW, Sepulveda AR. Evaluation of Mutational Testing of Pre-neoplastic Barrett's Mucosa by Next Generation Sequencing of FFPE Endoscopic Samples for Detection of Concurrent Dysplasia and Adenocarcinoma in Barrett's Esophagus, Journal of Molecular Diagnostics 2015; 25: 1-7. Link
- Hartman DJ, Krasinskas AM, Bista RK, Uttam S, Staton KD, Rizvi R, Slivka A, Brand RE, Liu Y. Assessment of nuclear nano-morphology marker to improve the detection of malignancy from bile duct biopsies, American Journal of Clinical Pathology 2014; 141:884-891. Link
- Liu Y, Uttam S, Alexandrov S, Bista R. Investigation of nanoscale structural alterations of cell nucleus as an early sign of cancer, BMC Biophysics 2014; 7: 1. Link
- Fasanella KE, Bista RK, Staton K, Rizvi S, Uttam S, Zhao C, Sepulveda A, Brand RE, McGrath K, and Liu Y. Nuclear Nano-architecture Markers of Gastric Cardia and Upper Squamous Esophagus Detect Esophageal Cancer “Field Effect”, Journal of Cancer 2013; 4(8): 626-634. Link
- Uttam S, Bista RK, Staton K, Alexandrov S, Choi S, Bakkenist CJ, Hartman DJ, Brand RE, and Liu Y. Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation, Biomedical Optics Express 2013; 4(4): 596-613. Link
- Uttam S, Alexandrov S, Bista RK, Liu Y. Tomographic imaging via spectral encoding of spatial frequency. Optics Express 2013; 21(6): 7488-7504. Link
- Alexandrov S, Uttam S, Bista RK, Liu Y. Spectral encoding of spatial frequency approach for characterization of nanoscale structures. Applied Physics Letters 2012; 101(4): 033702. Link PMC3411560
- Bista RK, Wang P, Bhargava R, Uttam S, Hartman DJ, Brand RE, Liu Y. Nuclear nano-morphology markers of histologically normal cells detect the "field effect" of breast cancer. Breast Cancer Research and Treatment 2012; 135(1): 115-124. Link
- Chen Y, Liang C-P, Liu Y, Fischer AH, Parwani AV, Pantanowitz L. Review of Advanced Imaging Techniques, Journal of Pathology Informatics, 2012; 3:22. Link
- Bista RK, Uttam S, Hartman DJ, Qiu W, Yu J, Zhang L, Brand RE and Liu Y. Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model, Journal of Biomedical Optics, 2012; 17(6): 066014. Link PMC3382352
- Alexandrov S, Uttam S, Bista RK, Zhao C, Liu Y. Real-time quantitative visualization of 3D structural information, Optics Express, 2012; 20(8): 9203-9214. Link Selected in Virtual Journal of Biomedical Optics.
- Uttam S, Bista RK, Hartman DJ, Brand RE and Liu Y. Correction of stain variations in nuclear refractive index of clinical histology specimens, Journal of Biomedical Optics, 2011; 16(11): 116013. Link PMC3221715.
- Alexandrov S, Uttam S, Bista RK, Liu Y. Spectral contrast imaging microscopy, Optics Letters, 2011; 36(11): 3323-3325. Link Selected in Virtual Journal of Biomedical Optics.
- Bista RK, Uttam S, Wang P, Staton K, Choi S, Bakkenist CJ, Hartman DJ, Brand RE and Liu Y. Quantification of Nanoscale Nuclear Refractive Index Changes during the Cell Cycle, Journal of Biomedical Optics (Letters), 2011; 16(7): 070503. Link PMC3146546 Selected in Virtual Journal of Biological Physics Research (July 15, 2011).
- Fang C, Brokl D, Brand RE, Liu Y. A depth-selective fiber-optic probe for characterization of superficial tissue with a constant physical depth. Biomedical Optics Express, 2011; 2(4): 838-849. Link
- Bista, RK, Brentnall, TA, Bronner, MA, Langmead, CJ, Brand, RE, Liu Y. Using optical markers of non-dysplastic rectal epithelial cells to identify patients with ulcerative colitis (UC)-associated neoplasia. Inflammatory Bowel Disease, 2011; 17(12): 2427-2435. Link PMC3139749
- Wang P, Bista R, Khalbuss WE, Qiu W, Staton K, Zhang L, Brentnall TA, Brand RE, Liu Y. Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy. Journal of Biomedical Optics, 2010; 15:066028. Link PMC3025597 Selected in Virtual Journal of Biological Physics Research (January 1, 2011).
- Wang P, Bista RK, Qiu W, Khalbuss WE, Zhang L, Brand RE, Liu Y. An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy. Optics Express, 2010; 18(21): 21950-21958. Link
- Wang P, Bista R, Bhargava R, Brand RE, Liu Y. Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis, Optics Letters, 2010; 35 (17): 2840-2842. Link Selected in Virtual Journal of Biomedical Optics.
- Mahmoud BH, Ruvolo E, Hexsel CL, Liu Y, Owen MR, Kollias N, Lim HW, Hamzavi IH, Impact of long wavelength UVA and visible light on melanocompetent skin, Journal of Investigative Dermatolology, 2010; 130: 2092-2097. Link
- Subramanian H, Pradhan P, Liu Y,
Capoglu I, Li X, Rogers J, Heiftez A, Kunte D, Roy HR, Taflove A,
Backman V. Optical methodology for detecting histologically unapparent
nanoscale consequences of genetic alterations in biological cells. Proc
Nat Acad Sci, 2008; 105(51):20124-20129. Link
- Liu Y, Brand
RE, Turzhitsky V, Kim YL, Roy HK, Hasabou N, Sturgis C,
Shah D, Hall C, Backman V. Optical markers in duodenal mucosa predict
the presence of pancreatic cancer, Clin Cancer Res. 2007;13(15 Pt
1):4392-9. Link (Featured article: Editoral) National Science Foundation Press Release
- Liu Y, Li X,
Kim YL, Backman V. Elastic backscattering spectroscopic microscopy. Opt
Letters. 2005;30(18):2445-7. Link
- Turzhitsky V, Liu Y, Hasabou N, Goldberg M, Roy HK, Backman V, Brand R. Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa. Dis Markers, 2009; 25:313-321. PMC2730822
- Subramanian H, Pradhan P, Liu Y, Capoglu I, Rogers J, Roy H, Brand R, Backman V, Partial wave microscopic spectroscopy detects sub-wavelength refractive index fluctuations: an application to cancer diagnosis, Opt Letters. 2009; 34(4): 518-520. PMC2701738
- Wali RK, Roy HK, Kim YL, Liu Y,
Goldberg MJ, Turzhitsky V,
and Backman V. Increased microvascular blood content is an early event
in colon carcinogenesis. Gut, 2005;54(5):654-60. Link
- Roy HK, Liu Y,
Wali RK, Kim YL, Kromin A, Goldberg MJ, Backman V.
Four-dimensional elastic light-scattering fingerprints as preneoplastic
markers in the rat model of colon carcinogenesis, Gastroenterology.
- Liu Y, Kim YL,
Li X, Backman V. Investigation of depth
selectivity of polarization gating for tissue characterization. Opt
Express. 2005; 13(2):526-33. Link
- Liu Y, Kim YL,
Backman V. Development of a bioengineered tissue
model and its application in the investigation of the depth selectivity
of polarization gating. Appl Opt. 2005; 44(12): 2288-99. Link
- Allen J, Liu Y,
Kim YL, Turzhitsky VM, Backman V, Ameer GA. Spectroscopic translation
of cell-material interactions, Biomaterials. 2007;28:162-74. Link
- Roy HK, Kim YL, Liu Y,
Wali RK, Goldberg MJ, Turzhitsky V, Horwitz J, Backman V.
Risk-stratification of colon carcinogenesis through Enhanced
Backscattering (EBS) spectroscopy analysis of the uninvolved colonic
mucosa. Clin Cancer Res. 2006;12(3 Pt 1):961-8. Link
- Xia X, Liu Y,
Backman V, Ameer G. Engineering sub-100 nm multi-layer nanoshells. Nanotechnol. 2006;17:5435-40. Link
- Kim YL, Liu Y,
Turzhitsky VM, Wali RK, Roy HK, and Backman V. Depth-resolved
low-coherent backscattering in tissue. Opt Letters 2005;30(7):741-3. Link
- Kim YL, Liu Y,
Wali RK, Roy HK, Backman V. Low-coherent backscattering spectroscopy
for tissue characterization. Appl Opt. 2005;44(3):366-77. Link
- Kim YL, Liu Y,
Turzhitsky V, Roy HK, Wali RK and Backman V. Coherent backscattering
spectroscopy. Opt Letters. 2004;29(16):1906-8. Link
- Kim YL, Liu Y,
Wali RK, Roy HK, Goldberg MJ, Kromin A, Chen K and Backman V.
Simultaneous measurement of angular and spectral properties of light
scattering for characterization of tissue microarchitecture and its
alteration in early precancer, IEEE J Sel Top Quantum Electron.
- Turzhitsky V, Gomes AJ, Kim YL, Liu
Y, Kromine A, Rogers JD, Jameel M, Roy HK, Backman V. Measuring Mucosal Blood Supply in vivo with a Polarization Gating Probe. Appl Optics, 2008; 47: 6046-6057.
- Roy HK, Turzhitsky V, Kim YL, Goldberg MJ, Muldoon JP, Liu Y, Brand RE, Hasabou N, Jameel
M, and Backman V. Spectral slope from the endoscopically-normal mucosa
predicts concurrent colonic neoplasia: A pilot ex-vivo clinical study. Dis Colon Rectum, 2008; 51: 1381-1386.
- Roy HK, Wali RK, Kim YL, Liu Y,
Hart J, Kunte DP, Koetsier
JL, Goldberg MJ, Backman V. Inducible Nitric Oxide Synthase (iNOS)
Mediates the Early Increase of Blood Supply (EIBS) in a Pre-dysplastic
Stage of Colon Carcinogenesis, FEBS Lett. 2007; 581(20): 3857-62.
- Figueiredo R, Backman V, Liu Y,
Paladugula J. Architecture
and performance of a grid-enabled lookup-based biomedical optimization
application: Light scattering spectroscopy. IEEE Trans Inf Technol
- Roy HK,
Turzhitsky V, Kim YL, Goldberg MJ, Muldoon JP, Liu Y, Brand RE, Hasabou
N, Jameel M, and Backman V. Spectral slope from the
mucosa predicts concurrent colonic neoplasia: A pilot ex-vivo clinical
Rectum, 2008; 0:
- Kim YL,
Turzhitsky V, Liu Y, Roy HK,
Wali RK, Subramanian H, Pradhan P, and
Backman V. Low-coherence enhanced backscattering (LEBS): Principles and
applications for colon cancer screening. J Biomed Opt.
- Roy HK, Kunte
DP, Koetsier JL, Hart J, Kim YL, Liu Y,
Bissonnette M, Goldberg MJ,
Backman V, Wali RK. Chemoprevention of colon carcinogenesis by
glycol: suppression of epithelial proliferation via modulation of
SNAIL/B-catenin signaling. Mol Cancer Ther. 2006;5(8):2060-69.
- Gong J, Liu B,
Kim YL, Liu Y, Li X, Backman
V. Wavelength synthesis for optimizing the
resolution of optical coherence tomography, Opt Express. 2006;
- Subramanian H,
P. Prabhakar, Kim YL, Liu Y,
Li X, and Backman V. Modeling low-coherence
enhanced backscattering using Monte Carlo simulation.
Appl Opt. 2006;45(24):6292-300.
- Kim YL, Pradhan
P, Subramanian H, Liu Y, Kim
MH, Backman V. Origin of low-coherence
enhanced backscattering. Opt Letters. 2006;31(10):1459-61.
- Chen K, Liu
Y, Ameer G, Backman V. Optimal design of structured nanospheres
ultra-sharp light scattering resonances as molecular imaging
Biomed Opt. 2005;10(2):024005.
- Roy HK, Kim YL,
Wali RK, Liu Y, Koetsier JL,
Kunte DP, Goldberg MJ, and Backman V.
Spectral markers in preneoplastic intestinal mucosa: An accurate
tumor risk in the MIN mouse, Cancer Epidemiol Biomarkers Prev. 2005;14(7):1639-45.
- Roy HK, Iversen
P, Hart J, Liu Y, Koetsier JL,
Kim YL, Kunte DP, Madugula M, Backman V,
Wali RK. Downregulation of SNAIL suppresses MIN mouse tumorigenesis:
of apoptosis, proliferation and fractal dimension. Mol Cancer Ther. 2004;3(9):1159-65.
- Zhu X-Q, Cao L, Liu Y, Yang Y, Lu J-Y, Wang
J-S, Cheng J-P. Thermodynamics and Kinetics
of the Hydride-Transfer Cycles for 1-Aryl-1,4-dihydronicotinamide and
1,2-Dihydroisome. Chem Eur J.
- Zhu X-Q, Liu
Y, Zhao B-J, Cheng J-P. An old but simple and efficient method
the oxidation mechanism of NAD(P)H model by cations
2-methyl-5-nitroisoquinolium, tropylium, and xanthylium in aqueous
Org Chem. 2001;66(2):370-75.
- Zhu X-Q, Zou H,
Yuan P, Liu Y, Cao L, Cheng
J-P. A detailed investigation into the
oxidation mechanism of Hantzsch by ethyl a-cyanocinnamates and
benzylidenemalononitriles. J Chem Soc
Perkin Trans. 2. 2000;9:1857-61.
Current Lab Members
Research Associate: Shikar, Ph.D.; Jiauquan Xu, Ph.D.
Postdoctoral Associate: Hoa V Pham, Ph.D.; Hongqiang Ma, Ph.D.
Graduate Student: Jingyi Jin
Current Research Sponsors
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