Engineering biophysical microtechnologies for hematologic applications in health and disease
工程生物物理微技术在健康和疾病中的血液学应用
基本信息
- 批准号:10350610
- 负责人:
- 金额:$ 76.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-22 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AddressAdoptedBiochemicalBiocompatible MaterialsBiological AssayBiological MarkersBiologyBiomedical EngineeringBiophysicsBloodBlood CirculationBlood PlateletsBlood VesselsCell CommunicationCellsClinicalClinical EngineeringClinical assessmentsCollagenComplexDiagnosticDiagnostic EquipmentDiseaseDisease modelDrug Delivery SystemsEndotheliumEngineeringEnvironmentExtravasationFunctional disorderGenesGoalsHealthHematological DiseaseHematologyHemorrhageHemostatic functionHydrogelsImmuneIn VitroLaboratoriesLeukocyte RollingMechanicsMedicineMicrofluidicsModelingMolecular BiologyPatientsPhysiciansPhysicsPhysiologicalPlatelet aggregationPlayProcessResearchScientistSickle Cell AnemiaSignal PathwaySystemTechnologyTherapeuticThrombocytopeniaThrombosisTrainingTranslatingTranslationsWorkbasebench to bedsideclinical diagnosticsdrug discoveryendothelial dysfunctionimprovedin vitro Modelinterdisciplinary approachinterestinventionmicrodevicenanoscalenanosystemsnew technologynovelorgan on a chippre-clinicalprogramstechnology developmenttool
项目摘要
Project Summary/Abstract
Complex biophysical cellular interactions are integral to many hematological processes ranging from platelet
aggregation to leukocyte rolling and extravasation through the endothelium. While molecular biology has led to
the discovery of numerous causative genes and associated biochemical signaling pathways, that is only part of
the picture, analogous to knowing only the actors in a play without knowing the plot. To fully comprehend how
these cellular machines in our blood work in concert in the dynamic environment of the circulation and how these
physical interactions go awry during disease states requires physical tools that operate at the cellular and
subcellular scales. With my background as a “physician-scientist-engineer” trained in clinical hematology and
bioengineering with specific focuses in micro/nanosystems technologies, microfluidics, and cellular mechanics,
my laboratory has steadily merged these fields together to develop tools to answer biophysical hematologic
questions that were previously technologically infeasible, which we then immediately translate to my patients'
bedsides. With specific focuses on hematologic processes and diseases such as hemostasis, thrombosis and
sickle cell disease, our laboratory has leveraged our unique combined clinical and engineering expertise to invent
groundbreaking microtechnologies that either function as in vitro models of hematologic processes and disease
that are more physiologically relevant than current systems or enable answering specific biophysical questions
in hematology that current systems are incapable of. More specifically, we have developed: 1) “organ-on-chip”
technologies to enable vascularized microfluidic models of the microvasculature that function as physiologically
relevant models of hemostasis, thrombosis, and sickle cell disease pathophysiology and 2) microengineered
platforms to study the cellular mechanics of how platelets respond to their biophysical microenvironment.
Collectively, our microtechnologies have not only led to groundbreaking research that have addressed questions
in hematology that were not answerable with current assays, but also serve as drug discovery platforms,
precursor technologies for novel diagnostic devices, and even paradigm-shifting drug delivery strategies. Moving
forward, our research program progresses both in terms of technology development and application thereof,
from asking basic impactful questions as well as translation towards the patient. Examples of the former involve
incorporating more complex microengineered features into our microfluidics, such as mechanical components
and novel biomaterials, to enable an “endothelialized” bleeding model to study all of the principal components of
hemostasis in vitro and a collagen hydrogel-based microvasculature-on-a-chip to investigate how cell-cell
interactions in sickle cell disease causes endothelial dysfunction, respectively. On the other hand, we are also
now applying our existing microtechnologies as biophysical biomarkers of hematologic diseases such as immune
thrombocytopenia. Overall, our laboratory's unique “basement-to-bench-to-bedside” approach will not only will
impact hematology research, but most importantly, improve the lives of my patients.
项目总结/摘要
复杂的生物物理细胞相互作用是许多血液学过程的组成部分,
聚集至白细胞滚动和通过内皮外渗。虽然分子生物学已经导致了
许多致病基因和相关的生化信号通路的发现,这只是部分
这就好比只知道戏剧中的演员而不知道情节。为了充分理解
我们血液中的这些细胞机器在循环的动态环境中协同工作,
在疾病状态期间,物理相互作用出错需要在细胞和
亚细胞鳞片我的背景是一名“医生-科学家-工程师”,接受过临床血液学培训,
生物工程,特别关注微/纳米系统技术,微流体和细胞力学,
我的实验室已经稳步地将这些领域融合在一起,开发工具来回答生物物理血液学
这些问题以前在技术上是不可行的,然后我们立即将其转化为我的病人的问题。
床边特别关注血液学过程和疾病,如止血、血栓形成和
镰状细胞病,我们的实验室利用我们独特的结合临床和工程专业知识,
开创性的微型技术,无论是作为血液过程和疾病的体外模型,
比当前系统更具有生理相关性或能够回答特定的生物物理问题
目前的系统无法做到的。更具体地说,我们开发了:1)“器官芯片”
使微血管系统的血管化微流体模型能够在生理上起作用的技术
止血、血栓形成和镰状细胞病病理生理学的相关模型和2)微工程
研究血小板如何响应其生物物理微环境的细胞力学平台。
总的来说,我们的微技术不仅带来了突破性的研究,
在血液学中,不能用当前的分析来回答,但也可以作为药物发现平台,
新型诊断设备的前体技术,甚至是改变范式的药物输送策略。移动
今后,我们的研究计划在技术开发和应用方面都取得了进展,
从提出基本的有影响力的问题以及向患者翻译。前者的例子包括
将更复杂的微工程特征整合到我们的微流体中,例如机械组件,
和新的生物材料,使“内皮化”出血模型能够研究所有的主要成分,
体外止血和基于胶原水凝胶微血管芯片研究细胞-细胞
镰状细胞病中的相互作用分别导致内皮功能障碍。另一方面,我们也
现在,我们将现有的微技术应用于血液病的生物物理生物标志物,
血小板减少症。总的来说,我们实验室独特的“地下室到工作台到床边”的方法不仅将
影响血液学研究,但最重要的是,改善我的病人的生活。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Wilbur A Lam其他文献
Effect of Epitope Specific Antibodies on Single Platelet Physiology with Implications for Immune Thrombocytopenia Purpura
- DOI:
10.1182/blood-2022-159547 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Nina Shaver;Oluwamayokun Oshinowo;Meredith E. Fay;David R. Myers;Wilbur A Lam - 通讯作者:
Wilbur A Lam
Wilbur A Lam的其他文献
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{{ truncateString('Wilbur A Lam', 18)}}的其他基金
Engineering biophysical microtechnologies for hematologic applications in health and disease
工程生物物理微技术在健康和疾病中的血液学应用
- 批准号:
10579951 - 财政年份:2019
- 资助金额:
$ 76.96万 - 项目类别:
Engineering biophysical microtechnologies for hematologic applications in health and disease
工程生物物理微技术在健康和疾病中的血液学应用
- 批准号:
9898450 - 财政年份:2019
- 资助金额:
$ 76.96万 - 项目类别:
SBIR phase II: A personalized, non-invasive hemoglobin level monitoring and management platform for chronic anemia patients.
SBIR II 期:针对慢性贫血患者的个性化、无创血红蛋白水平监测和管理平台。
- 批准号:
10458078 - 财政年份:2018
- 资助金额:
$ 76.96万 - 项目类别:
Emergency COVID-19 Variant Supplement for Atlanta Center for Microsystems Engineered Point-of-Care Technologies (ACME POCT)
亚特兰大微系统工程护理点技术中心 (ACME POCT) 的紧急 COVID-19 变异补充品
- 批准号:
10476947 - 财政年份:2018
- 资助金额:
$ 76.96万 - 项目类别:
Atlanta Center for Microsystems Engineered Point-of-Care Technologies (ACME POCT)
亚特兰大微系统工程护理点技术中心 (ACME POCT)
- 批准号:
10715493 - 财政年份:2018
- 资助金额:
$ 76.96万 - 项目类别:
SBIR phase II: A personalized, non-invasive hemoglobin level monitoring and management platform for chronic anemia patients.
SBIR II 期:针对慢性贫血患者的个性化、无创血红蛋白水平监测和管理平台。
- 批准号:
10325763 - 财政年份:2018
- 资助金额:
$ 76.96万 - 项目类别:
Redefining Clinical Viscosity in Sickle Cell Diseaseby Leveraging Microfluidic Technologies
利用微流体技术重新定义镰状细胞病的临床粘度
- 批准号:
10022309 - 财政年份:2018
- 资助金额:
$ 76.96万 - 项目类别:
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