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Jacob S Brenner, MD, PHD

Jacob S Brenner, MD, PHD Physician

Assistant Professor of Pharmacology Assistant Professor of Medicine

Dr. Brenner is employed by Penn Medicine.

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About Dr. Jacob S. Brenner

Dr. Brenner is a critical care physician.  He attends in the medical ICU at the Hospital of the University of Pennsylvania.  His research is developing nanomedicine for acute critical illnesses, including ARDS, stroke, sepsis, and more.

Clinical Specialties


  • Pulmonary Medicine

Programs & Centers:

Board Certification:

  • Critical Care Medicine, 2015
  • Internal Medicine, 2013
  • Pulmonary Disease, 2014

Clinical Expertise:

  • Acute Bronchitis
  • Acute Decompensated Heart Failure
  • Acute Kidney Injury
  • Acute Respiratory Distress Syndrome (ARDS)
  • Advanced Diagnostic Bronchoscopy
  • Airway Disorders
  • Airway Obstruction
  • Allergic Pneumonitis
  • Allergic Wheezing
  • Arterial Line Placement
  • Asbestosis
  • Aspiration Pneumonitis
  • Asthma
  • Asthmatic Bronchitis
  • Atelectasis
  • Atrial Fibrillation (Afib)
  • Autoimmune Pleuritis
  • Bilevel Positive Airway Pressure
  • Bronchiectasis
  • Bronchitis
  • Bronchoscopy
  • Bronchospasm
  • Cardiac Arrest
  • Cardiogenic Shock
  • Central Line Insertion
  • Chest Wall Abscess
  • Chronic Bronchitis
  • Chronic Lung Disease
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Chronic Respiratory Failure
  • Chronic Thromboembolic Pulmonary Hypertension
  • Continuous Positive Airway Pressure (CPAP)
  • Cryptogenic Organizing Pneumonia
  • CT Scan (Computed Tomography)
  • Cystic Fibrosis
  • Delirium
  • Diabetic Ketoacidosis
  • Dialysis
  • Dialysis Catheter
  • Diaphragm Injury
  • Drug-Induced Pulmonary Disease
  • Dyspnea
  • Dyspnea On Exertion
  • Electrolyte Disorders
  • Emphysema
  • Empyema
  • Epiglottitis
  • Epilepsy
  • Exercise Intolerance
  • Flu (Influenza)
  • Gastrointestinal Bleeding
  • Goodpasture Syndrome
  • Hemoptysis
  • Hepatic Encephalopathy
  • Hepatic Hydrothorax
  • Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)
  • Hypercarbia
  • Hypotension
  • Hypoventilation Syndrome
  • Hypoxia
  • Inhaled Nitric Oxide
  • Interstitial Lung Disease
  • Kidney Failure
  • Laryngotracheitis
  • Liver Failure
  • Low Oxygen Level
  • Lung Abscess
  • Lung Disease
  • Lung Infiltrate
  • Lung Transplantation
  • Lung Tumors
  • Mechanical Ventilation
  • Needle Procedure
  • Occupational Lung Disease
  • Pleural Diseases
  • Pleural Effusion (Fluid in the Lung)
  • Pleural Thickening
  • Pleurisy
  • Pleuritic Pain
  • Pneumonia
  • Pneumonitis
  • Pulmonary and Cardiac Rehabilitation
  • Pulmonary Arterial Hypertension
  • Pulmonary Bullae
  • Pulmonary Complications of Neurological Diseases
  • Pulmonary Embolism (Pulmonary Embolus)
  • Pulmonary Fibrosis
  • Pulmonary Hemorrhage
  • Pulmonary Hypertension
  • Pulmonary Infections
  • Pulmonary Sarcoid
  • Pulmonary Therapy
  • Radiation Pneumonitis
  • Reactive Airway Disease
  • Recurrent Lung Infections
  • Respiratory Failure
  • Restrictive Lung Disease
  • Sepsis (Septicemia)
  • Severe Acute Respiratory Syndrome
  • Silicosis
  • Sleep Apnea
  • Sleep Disorders
  • Smoking related Disease
  • Spirometry
  • Sputum Production
  • Status Epilepticus
  • Stridor
  • Tracheal Mass
  • Tracheal Stenosis
  • Tracheobronchitis
  • Tracheomalacia
  • Tuberculosis (TB)
  • Ventilator Dependent
  • Wheezing
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Practice Locations and Appointments

Insurance Accepted

  • Aetna US Healthcare
  • Amerihealth Caritas
  • Amerihealth Caritas Medicare
  • Cigna
  • Cigna HealthSpring
  • Clover Health Plan
  • CVS Health
  • Devon Health Services (Americare)
  • eLAP Services
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Homestead Smart Health Plans
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Keystone First Medicare
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Health and Wellness (Centene) Medicare
  • PA Medicaid
  • PA Medicare
  • Preferred Health Care/LGH
  • Provider Partners Health Plan
  • Rail Road Medicare / Palmetto GBA
  • Remedy Partners at Penn Medicine
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan
  • Veterans Choice Program

Education and Training

Medical School: Stanford University
Medical School: Stanford University School of Medicine
Residency: Stanford University Medical Center
Fellowship: Hospital of the University of Pennsylvania


American Thoracic Society, National Society for Critical Care Medicine, National

Hospital Affiliation

Dr. Brenner is employed by Penn Medicine.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.
  • Penn Medicine Rittenhouse Long-Term Acute Care Hospital: Has privileges to treat patients in the hospital.
  • Penn Presbyterian Medical Center: Has privileges to treat patients in the hospital.
  • Pennsylvania Hospital: Has privileges to treat patients in the hospital.


Description of Research Expertise:

Dr. Brenner’s lab ( 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 (, 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.

Please join the Brenner lab in the fight, building technologies to defeat these terrible diseases!

Selected Publications:

Marcos-Contreras OA, Brenner JS, Kiseleva RY, Zuluaga-Ramirez V, Greineder CF, Villa CH, Hood ED, Myerson JW, Muro S, Persidsky Y, Muzykantov VR: Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted vs untargeted nanocarriers in the inflamed brain J Control Release 301 : 54-61,2019.

Paris AJ, Guo L, Dai N, Katzen JB, Patel PN, Worthen GS, Brenner JS: Using selective lung injury to improve murine models of spatially heterogeneous lung diseases PLoS One 14 (4): 2019.

Parhiz H, Shuvaev VV, Pardi N, Khoshnejad M, Kiseleva RY, Brenner JS, Uhler T, Tuyishime S, Mui BL, Tam YK, Madden TD, Hope MJ, Weissman D, Muzykantov VR.: PECAM-1 directed re-targeting of exogenous mRNA providing two orders of magnitude enhancement of vascular delivery and expression in lungs independent of apolipoprotein E-mediated uptake. J Control Release 10 : 106-115,2018.

Muzykantov VR, Brenner JS: Vascular Immunotargeting: Take the Highway to the First Exit. Hepatology 68 (5): 1672-1674,2018.

Brenner JS*, Pan D*, Myerson J*, Marcos-Contreras OA*, et al: RBC-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude Nature Communications 9 (1): 2648,2018.

Parhiz H, Khoshnejad M, Myerson JW, Hood E, Patel PN, Brenner JS, Muzykantov VR.: Unintended effects of drug carriers: Big issues of small particles. Adv Drug Deliv 130 : 90-112,2018.

Pan Daniel C, Myerson Jacob W, Brenner Jacob S, Patel Priyal N, Anselmo Aaron C, Mitragotri Samir, Muzykantov Vladimir: Nanoparticle Properties Modulate Their Attachment and Effect on Carrier Red Blood Cells. Scientific reports 8 (1): 1615,2018.

Brenner Jacob S, Kiseleva Raisa Yu, Glassman Patrick M, Parhiz Hamideh, Greineder Colin F, Hood Elizabeth D, Shuvaev Vladimir V, Muzykantov Vladimir R: The new frontiers of the targeted interventions in the pulmonary vasculature: precision and safety (2017 Grover Conference Series). Pulmonary circulation 8 (1): 2045893217752329,2018.

Khoshnejad Makan, Brenner Jacob S, Motley William, Parhiz Hamideh, Greineder Colin F, Villa Carlos H, Marcos-Contreras Oscar A, Tsourkas Andrew, Muzykantov Vladimir R: Molecular engineering of antibodies for site-specific covalent conjugation using CRISPR/Cas9. Scientific reports 8 (1): 1760,2018.

Brenner JS, Bhamidipati K, Glassman P, Ramakrishnan N, Jiang D, Paris AJ, Myerson JW, Pan DC, Shuvaev VV, Villa C, Hood ED, Kiseleva R, Greineder CF, Radhakrishnan R, Muzykantov VR: Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions. Nanomedicine 13 (4): 1495-1506,2017.

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Academic Contact Info

3400 Spruce Street
08028 Maloney Building

Philadelphia, PA 19104
Phone: (215) 662-2222