Lin Lab

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Phone: 617-643-3531

The main research focus of our group is to develop minimally invasive optical techniques for in vivo imaging and monitoring of cells and tissues as well as therapeutic applications of lasers. The diagnostic techniques will help to answer important biological questions, such as:

  • In-vivo monitoring of cell trafficking in circulation
  • Imaging of vasculature and microenvironment in tissue
  • Interaction of cells with microenvironment

The therapeutic techniques allow us to target cellular and subcellular structures by means of selective absorption of endogenous or exogenous chromophores. Selective targeting may be helpful for treating various pathologies, such as retinal diseases or destruction of tumors, without causing adverse side effects to healthy tissue.

Recent Publications

  • Christodoulou C, Spencer JA, Yeh SA, Turcotte R, Kokkaliaris KD, Panero R, Ramos A, Guo G, Seyedhassantehrani N, Esipova TV, Vinogradov SA, Rudzinskas S, Zhang Y, Perkins AS, Orkin SH, Calogero RA, Schroeder T, Lin CP, Camargo FD Live-animal imaging of native haematopoietic stem and progenitor cells. Nature. 2020;578(7794):278-283 - PMID: 32025033 - PMCID: PMC7021587 - DOI: 10.1038/s41586-020-1971-z

  • Park SY, Matte A, Jung Y, Ryu J, Wilson AB, Han EYA, Liu M, Carbone C, Melisi D, Nagasawa T, Locascio JJ, Lin CP, Silberstein LE, De Franceschi L Pathologic angiogenesis in the bone marrow of humanized sickle cell mice is reversible by blood transfusion. Blood. 2020;:ePub - PMID: 31990287 - DOI: 10.1182/blood.2019002227

  • Patil R, Tan X, Bartosik P, Detappe A, Runnels JM, Ghobrial I, Lin CP, Niedre M Fluorescence monitoring of rare circulating tumor cell and cluster dissemination in a multiple myeloma xenograft model in vivo. J Biomed Opt. 2019;24(8):1-11 - PMID: 31456386 - PMCID: PMC6983486 - DOI: 10.1117/1.JBO.24.8.085004

  • Bassir SH, Garakani S, Wilk K, Aldawood ZA, Hou J, Yeh SA, Sfeir C, Lin CP, Intini G Prx1 Expressing Cells Are Required for Periodontal Regeneration of the Mouse Incisor. Front Physiol. 2019;10:591 - PMID: 31231227 - PMCID: PMC6558369 - DOI: 10.3389/fphys.2019.00591

  • Bassir SH, Garakani S, Wilk K, Aldawood ZA, Hou J, Yeh SA, Sfeir C, Lin CP, Intini G Prx1 Expressing Cells Are Required for Periodontal Regeneration of the Mouse Incisor. Front Physiol. 2019;10:591 - PMID: 31231227 - PMCID: PMC6558369 - DOI: 10.3389/fphys.2019.00591

  • More publications ...

Research projects

TECHNOLOGY
Multimodal Microscopy

Imaging modalities such as confocal reflectance microscopy, fluorescence by single- or two-photon excitation, second harmonic generation and coherent anti-Stokes Raman spectroscopy (CARS) provide different contrast mechanisms that can be combined to give structural, functional and molecular information of living tissue. Our group has developed a multimodal microscope in which up to three of these imaging modalities can be realized simultaneously. Images are acquired at video rate, which allows real-time monitoring of fast events in the living tissue.

Adaptive Optics

Ophthalmic imaging resolution suffers from aberrations present in the eye. With the introduction of an adaptive optics (AO) system into a scanning laser ophthalmascope (SLO) one can achieve the best possible resolution for the system. We have implemented such an AO system into a SLO designed for imaging the mouse retina.

In vivo flow cytometry
Images of GTP labeled microglia in the living mouse retina.
(a) Aberrated image (AO system off).
(b) Corrected image (AO system running)
Our group has developed an in vivo flow cytometer, based on confocal design. Contrary to the conventional flow cytometer, the in vivo flow cytometer can provide real-time detection and quantitative information on fluorescently labeled cells while in circulation in a live animal model. As the labeled cells pass through a slit of light focused across a blood vessel, fluorescence is excited. Its confocal detection makes it possible to observe the cell population of interest without the need to extract a blood sample. Furthermore, the same cell population can be tracked continuously and over long periods of time to examine the dynamic changes in the circulation of different types of cells in the same animal. The in vivo flow cytometer has been used to measure the circulation lifetime of different tumor cells and leukocyte populations in the peripheral circulation in response to immunological stress or therapeutic manipulation.
Cells (circles) flow through the blood vessel as shown. A slit of excitation light (green box) illuminates passing cells. When a fluorescently labeled cell passes through the “slit” it emits light.
Sample flow cytometer trace. (Novak et al, Opt. Lett. 2004)
BIOLOGICAL STUDIES
Vascular Biology
Vascular permeability

Role of IKK-ß in Akt activation and vascular permeability. Evans blue dye was injected into a transgenic (TG) and control mouse (CM). Images were taken at 1:30 and 10:00 minutes after injection. Increased vessel leakage was shown in the TG mouse, due to the deletion of IKK-ß, which reduces activation of Akt, and increases vascular permeability.

Leukocyte-endothelial interaction


Comparison of the adhesion of native blood leukocytes (NL) and C-GSF mobilized peripheral blood leukocytes (ML). An image comparing the adhesion of these cells in the vascular endothelium is shown along with a measurement of the number of adhered cells.


Cancer
Leukemia
Multiple Myeloma
Transplantation Immunology
T cell conversion

A) Image of regulatory T cells (FOXP3-GFP) that have migrated to the islet graft after adoptive transfer. B) Image of effector T cells (U-DsRed) acquired at the same time as A. C) Co-registered image revealing natural regulatory T cells (green), effector T cells (red), and a converted regulatory T cell (yellow).

Simultaneous, independent detection of GFP+ regulatory T cells (blue) and DSRed+ naïve T cells (red).

Graft versus Host Disease

Investigation of T cell migration in graft versus host disease (GVHD). Images of transplanted T cells near a hair follicle in a (A) freshly irradiated mouse and (B) mixed Chimera (MC) mouse 5 days after transplantation. T cell counts after 5 and 12 days in the irradiated mouse (C) and MC (D). Images of T cells 5 days after transplantation near postcapillary venules in the freshly irradiated mouse (E) and the MC (F).

Stem Cell Biology
Mesenchymal Stem Cells

In vivo confocal and 2-photon microscopy demonstrating the extravasation of FTVI treated MSCs and subsequent migration to the bone surface in the mouse bone marrow after adoptive transfer. DiD-labeled MSCs (red), primarily line the vessel walls (green) at 1 hr after transfer A), whereas at 24 hrs B), the MSCs show a marked increase in extravasation (arrow). Second Harmonic Generation microscopy of bone (collagen, blue) reveals the close juxtaposition between the cells and the bone after 9 days. The bone image in D) is 10µm above the image in C). Bar=50µm for A-B) and 100µm for C-D).

Hematopoietic stem cells
Combined second harmonic and two-photon microscopy image, showing the bone (blue) and Ikaros GFP cells filling the BM. Bar = 50 µm.
Combined second harmonic and confocal microscopy image, showing a single DiD labeled LSK cells sitting on the endosteal surface of the bone (blue) 24 hours after transplantation.

News

2019-04-04: Three CSB researchers - Clemens Alt, PhD (Lin Lab), Cameron McAlpine, PhD and Shun He, PhD (Swirski Lab) - won Poster of Distinction award at the Annual Meeting of the MGH Scientific Advisory Committee (SAC). Congratulations!
2012-01-30: Clemens Alt, PhD won the 2012 Pascal Rol Award for Best Paper in Ophthalmic Technologies at the recent SPIE Photonics West, BiOS conference in San Francisco for his presentation and proceedings paper entitled "In vivo quantification of microglia dynamics with a scanning laser ophthalmoscope in a mouse model of focal laser injury". (pdf)
2010-06-29: "Color-coded Mouse Sheds Light on Transplant Tolerance" - work of Charles Lin's Lab is featured in the Harvard Focus. (pdf)