基本信息
浏览量:0
职业迁徙
个人简介
Description of Clinical Expertise
Dr. Brenner attends in the Medical Intensive Care Unit (MICU) at the Hospital of the University of Pennsylvania. He is board certified and fellowship trained in critical care.
Description of Other Expertise
Dr. Brenner teaches medical entrepreneurship at Penn, as part of Penn Health-Tech (Penn's medical device center). Dr. Brenner previously started 3 funded medical device companies, one of which has already achieved FDA approval for a first-in-class device.
Description of Research Expertise
Dr. Brenner’s lab (www.brennerbioengineeringlab.com) engineers new technologies for the diseases of Pulmonary & Critical Care Medicine (PCCM). PCCM encompasses both diseases of the lungs and acute critical illnesses (ACIs), which means all acutely life-threatening diseases, such as ARDS, stroke, sepsis, & more.
Dr. Brenner’s lab engineers technologies ranging from the macro-scale (devices you can hold), all the way down to the nano-scale (smaller than cells). On the macro-scale, Dr. Brenner has spun out 3 funded medical device companies, including one with FDA approval, and his most recent one, RightAir (www.rightair.io/), is currently in clinical studies with its AIR-AD Vest to relieve shortness of breath in COPD patients.
The nano-scale is where Dr. Brenner’s lab spends most of their time, developing nanomedicine for acute critical illnesses (ACIs). ACIs are a huge class of diseases, accounting for costs that are 4% of the US GDP! Unfortunately, there are few if any disease-specific drugs, and the outcomes remain very poor.
In developing new approach for ACIs, it is notable that they all share 3 unique pharmacological challenges: 1) ACI patients are fragile, with multiple simultaneous organ systems perturbed, so they do not tolerate the off-target side effects of drugs (side effects in remote organs). 2) ACIs are heterogeneous, with multiple subgroups and cell types implicated, so therapy targeting a single pathway is unlikely to work. 3) These diseases are rapidly progressive, so each signaling pathway is active for only a short time window.
To solve these 3 pharmacological challenges and thereby create a platform technology for treating ACIs, the Brenner Lab has been developing VMNs (vascular-targeted, multi-drug-loaded nanocarriers). VMNs are ~100-nanometer drug carriers that when injected intravascularly concentrate strongly in the target organ, using a variety of targeting mechanisms explained below. By concentrating drugs in the diseased organ, VMNs eliminate the off-target side effects of cargo drugs, solving problem #1 above. By shuttling multiple drugs, they address multiple points of pathology, solving the heterogeneity problem (#2 above) and the issue that ACIs are rapidly progressive (#3). The lab chose vascular-targeting for VMNs because nearly all ACIs are vascular-oriented, with pathology largely residing in the blood vessels, in the form of inflammation, thrombosis, and ischemia. Additionally, intravascular access for infusing VMNs is easy in ACI patients, as they all have IVs, and it is common to put in intra-arterial (IA) catheters during procedures (e.g., for stroke and heart attack).
Dr. Brenner and his lab have created a number of targeting mechanisms for VMNs so that they can target any organ affected by ACIs, and address the VMNs to particular cell types. The first such technology, developed in the 1990s by Dr. Brenner’s former postdoc advisor and continued close collaborator, Dr. Vlad Muzykantov, involves conjugating to VMNs’ surface affinity moieties (e.g., antibodies and derivatives thereof) that bind to endothelial cells (see Dr. Brenner’s publications with PMIDs 28065731, 28304180). The second such technology Dr. Brenner co-developed is RBC-hitchhiking (RH), in which VMNs are adsorbed onto red blood cells, which facilitates transfer to the capillary endothelium, without needing antibodies (PMID 29992966). Combined with IA catheters, RH achieved the highest published levels of delivery to organs such as the kidney (for the ACI acute kidney injury) and brain (for treating stroke, where RH achieved >10x the brain delivery of the best prior technology). Finally, more recently, in unpublished work, the Brenner lab has developed a technology for targeting VMNs to resident leukocytes in organs affected by ACIs.
With this suite of targeting mechanisms, the Brenner lab is now identifying the optimal combinations of drugs to load into VMLs. The lab is interested in using computational techniques to predict the best drugs to load (PBPK modeling, network pharmacology), and then testing the drugs in multiple animal models of disease. The Brenner lab primarily uses rodent models, but in order to maximize translational potential, also employs large animal models (pigs) and even fresh, ex vivo human organs that have been rejected for transplant, usually because they are afflicted by the ACIs that are the lab’s focus (PMID 29992966). The goal is to develop VMNs for each ACI, and move them to patients by partnering with industry, which the Brenner lab already has done by forming a close collaboration with a pharmaceutical company in developing VMNs for ARDS.
Dr. Brenner attends in the Medical Intensive Care Unit (MICU) at the Hospital of the University of Pennsylvania. He is board certified and fellowship trained in critical care.
Description of Other Expertise
Dr. Brenner teaches medical entrepreneurship at Penn, as part of Penn Health-Tech (Penn's medical device center). Dr. Brenner previously started 3 funded medical device companies, one of which has already achieved FDA approval for a first-in-class device.
Description of Research Expertise
Dr. Brenner’s lab (www.brennerbioengineeringlab.com) engineers new technologies for the diseases of Pulmonary & Critical Care Medicine (PCCM). PCCM encompasses both diseases of the lungs and acute critical illnesses (ACIs), which means all acutely life-threatening diseases, such as ARDS, stroke, sepsis, & more.
Dr. Brenner’s lab engineers technologies ranging from the macro-scale (devices you can hold), all the way down to the nano-scale (smaller than cells). On the macro-scale, Dr. Brenner has spun out 3 funded medical device companies, including one with FDA approval, and his most recent one, RightAir (www.rightair.io/), is currently in clinical studies with its AIR-AD Vest to relieve shortness of breath in COPD patients.
The nano-scale is where Dr. Brenner’s lab spends most of their time, developing nanomedicine for acute critical illnesses (ACIs). ACIs are a huge class of diseases, accounting for costs that are 4% of the US GDP! Unfortunately, there are few if any disease-specific drugs, and the outcomes remain very poor.
In developing new approach for ACIs, it is notable that they all share 3 unique pharmacological challenges: 1) ACI patients are fragile, with multiple simultaneous organ systems perturbed, so they do not tolerate the off-target side effects of drugs (side effects in remote organs). 2) ACIs are heterogeneous, with multiple subgroups and cell types implicated, so therapy targeting a single pathway is unlikely to work. 3) These diseases are rapidly progressive, so each signaling pathway is active for only a short time window.
To solve these 3 pharmacological challenges and thereby create a platform technology for treating ACIs, the Brenner Lab has been developing VMNs (vascular-targeted, multi-drug-loaded nanocarriers). VMNs are ~100-nanometer drug carriers that when injected intravascularly concentrate strongly in the target organ, using a variety of targeting mechanisms explained below. By concentrating drugs in the diseased organ, VMNs eliminate the off-target side effects of cargo drugs, solving problem #1 above. By shuttling multiple drugs, they address multiple points of pathology, solving the heterogeneity problem (#2 above) and the issue that ACIs are rapidly progressive (#3). The lab chose vascular-targeting for VMNs because nearly all ACIs are vascular-oriented, with pathology largely residing in the blood vessels, in the form of inflammation, thrombosis, and ischemia. Additionally, intravascular access for infusing VMNs is easy in ACI patients, as they all have IVs, and it is common to put in intra-arterial (IA) catheters during procedures (e.g., for stroke and heart attack).
Dr. Brenner and his lab have created a number of targeting mechanisms for VMNs so that they can target any organ affected by ACIs, and address the VMNs to particular cell types. The first such technology, developed in the 1990s by Dr. Brenner’s former postdoc advisor and continued close collaborator, Dr. Vlad Muzykantov, involves conjugating to VMNs’ surface affinity moieties (e.g., antibodies and derivatives thereof) that bind to endothelial cells (see Dr. Brenner’s publications with PMIDs 28065731, 28304180). The second such technology Dr. Brenner co-developed is RBC-hitchhiking (RH), in which VMNs are adsorbed onto red blood cells, which facilitates transfer to the capillary endothelium, without needing antibodies (PMID 29992966). Combined with IA catheters, RH achieved the highest published levels of delivery to organs such as the kidney (for the ACI acute kidney injury) and brain (for treating stroke, where RH achieved >10x the brain delivery of the best prior technology). Finally, more recently, in unpublished work, the Brenner lab has developed a technology for targeting VMNs to resident leukocytes in organs affected by ACIs.
With this suite of targeting mechanisms, the Brenner lab is now identifying the optimal combinations of drugs to load into VMLs. The lab is interested in using computational techniques to predict the best drugs to load (PBPK modeling, network pharmacology), and then testing the drugs in multiple animal models of disease. The Brenner lab primarily uses rodent models, but in order to maximize translational potential, also employs large animal models (pigs) and even fresh, ex vivo human organs that have been rejected for transplant, usually because they are afflicted by the ACIs that are the lab’s focus (PMID 29992966). The goal is to develop VMNs for each ACI, and move them to patients by partnering with industry, which the Brenner lab already has done by forming a close collaboration with a pharmaceutical company in developing VMNs for ARDS.
研究兴趣
论文共 85 篇作者统计合作学者相似作者
按年份排序按引用量排序主题筛选期刊级别筛选合作者筛选合作机构筛选
时间
引用量
主题
期刊级别
合作者
合作机构
Serena Omo-Lamai,Marco E. Zamora, Manthan N. Patel,Jichuan Wu,Jia Nong,Zhicheng Wang,Alina Peshkova, Aparajeeta Majumder,Jilian R. Melamed, Liam S. Chase,Eno-Obong Essien,Drew Weissman,
ADVANCED MATERIALSpp.e2312026-e2312026, (2024)
ACS nano (2024)
Serena Omo-Lamai, Yufei Wang, Manthan N Patel, Eno-Obong Essien,Mengwen Shen, Aparajeeta Majumdar, Carolann Espy, Jichuan Wu, Breana Channer, Michael Tobin, Shruthi Murali, Tyler E Papp,
bioRxiv : the preprint server for biology (2024)
Journal of Colloid and Interface Science (2024): 1042-1055
Langmuir : the ACS journal of surfaces and colloidsno. 16 (2024): 8365-8372
Redox Biology (2024): 103185-103185
Critical care medicine (2024)
Anush Lingamoorthy,Amanda Watson,Korey Henderson,Ayan Mandal,David Gordon,Xiaonan Ma,James Weimer, Nagarajan Kandasamy,Jacob S. Brenner
CHASEpp.56-67, (2023)
Marco E. Zamora, Serena Omo-Lamai, Manthan N. Patel,Jichuan Wu,Evguenia Arguiri, Vladmir Muzykantov,Jacob Myerson,Oscar Marcos-Contreras,Jacob S. Brenner
biorxiv(2023)
Advanced NanoBiomed Researchno. 3 (2023): 2200106
加载更多
作者统计
合作学者
合作机构
D-Core
- 合作者
- 学生
- 导师
数据免责声明
页面数据均来自互联网公开来源、合作出版商和通过AI技术自动分析结果,我们不对页面数据的有效性、准确性、正确性、可靠性、完整性和及时性做出任何承诺和保证。若有疑问,可以通过电子邮件方式联系我们:report@aminer.cn